Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 Mar 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Amendments to the claims filed 16 Jul 2026 are acknowledged. Claims 1-27 are originally presented. Claim 28 is withdrawn.
Applicant’s election without traverse to Group I, drawn to claims 1-27, and to Species VI, drawn to claim 10, in the reply filed 16 Jul 2026 is acknowledged.
Claims 5-9, 11, and 14-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected election or species, there being no allowable generic or linking claim.
Claims 1-28 are pending. Claims 1-4, 10, 12-13, and 18-27 are considered on the merits.
Claim Objections
Claims 3, 10, and 18-19 are objected to because of the following informalities:
Regarding claims 3, 10, and 18, gene identifiers should be italicized.
Regarding claims 3 and 18, the gene name for AAMP should be corrected to "angio-associated migratory cell protein" and the gene name for DEFA5 should be corrected to "defensin alpha 5" (without the letter g).
Regarding claim 10, the gene identifier RPS27 is misspelled as "RSP27" in line 3.
Regarding claim 19, SEQ ID NO: 7 is misspelled as "SED ID NO: 7".
Appropriate correction is required.
Claims 4 and 19 are objected to because the claims do not conform to sequence rules requiring the use of "SEQ ID NO:" when reciting a sequence. See 37 CFR 1.821-1.825 and MPEP § 2422.01. Furthermore, SEQ ID NO: are merely identifiers of the sequences, not the sequences themselves. For example, the claims should recite "wherein each of the plural downstream/upstream translation control elements independently comprises a translation control element selected from the group consisting of the sequences set forth in SEQ ID NO: 8...".
Claim 4 is objected to as being dependent on a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper". Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The use of the term Moderna®, which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology, be capitalized wherever it appears and, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner that might adversely affect their validity as commercial marks.
The disclosure is objected to because of the following informalities:
The term nucleic is misspelled in the title on p. 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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.
Claims 23-26 are rejected under 35 U.S.C. § 112(a) as failing to comply with the written description requirement. The claims contain 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 at the time the application was filed had possession of the claimed invention.
Claim 23 is drawn to a nucleic acid encoding for a reporter protein, a marker, a selection protein, or a fragment thereof. The specification provides examples of reporter proteins, markers, and selection proteins (par. 101-102) and a skilled artisan would recognize the structure-function relationship between a nucleic acid coding region and the use of the encoded gene product, such as a protein or RNA, as a reporter, biomarker, or selection protein. However, a fragment of such a coding region, as claimed, does not necessarily have the same function as the whole gene product. The specification does not provide examples of fragments of a reporter protein, marker, or selection protein or contemplate how much of the coding region must be present to be regarded as a fragment, or what, if any, function must be retained by the fragment. Therefore, there is no structure-function relationship for a fragment of a reporter protein, marker, or selection protein by which a skilled artisan could envision the detailed structure of at least a representative number of species of each genera of coding region fragments.
Claims 24-25 are drawn to a nucleic acid encoding for an antigen or a fragment thereof. Claim 25 is further drawn to the antigen being a peptide of a pathogenic or tumor antigen, or a variant or a derivative thereof. Under the broadest reasonable interpretation, an antigen is any molecule or a portion thereof that can bind to an antibody or T-cell receptor. The specification provides examples of pathogenic antigens derived from pathogenic organisms (par. 105) and tumor-associated antigens (par. 106-107), and a skilled artisan would recognize the structure-function relationship between a nucleic acid coding region and an antigen. However, a variant or derivative of such a coding region, as claimed, does not necessarily have the same function as the whole gene product. The specification does not provide examples of a variant or derivative of an antigen or contemplate how much of the coding region must be present to be regarded as a variant or derivative, or what, if any, function must be retained by the variant or derivative. Therefore, there is no structure-function relationship for a variant or derivative of an antigen by which a skilled artisan could envision the detailed structure of at least a representative number of species of each genera of coding region variants or derivatives.
Claim 26 is drawn to a nucleic acid encoding for a peptide for disease treatment or a fragment thereof. A skilled artisan would recognize the structure-function relationship between a nucleic acid coding region and use of the encoded peptide for the intended use of disease treatment. However, a fragment of such a coding region, as claimed, does not necessarily have the same function as the whole gene product. The specification does not provide examples of fragments of a peptide for disease treatment or contemplate how much of the coding region must be present to be regarded as a fragment, or what, if any, function must be retained by the fragment. Therefore, there is no structure-function relationship for a fragment of a peptide for disease treatment by which a skilled artisan could envision the detailed structure of at least a representative number of species of each genera of coding region fragments.
The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure “indicates that the patentee has invented species sufficient to constitute the gen[us].” See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) (“[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated.”). The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, such as physical and/or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show that the inventor was in possession of the claimed genus. See MPEP § 2163(II)(A).
Friedberg (I. Friedberg, Brief Bioinform, 2006) teaches that prediction of function of a protein with high sequence similarity or identity to a protein with known function is unreliable (p. 227). Furthermore, Friedberg teaches that protein rely on only a few amino acids in a domain carry out a specific function; therefore, even small variations or missing components of those functional domains can alter protein function (p. 231). Therefore, a skilled artisan would recognize that a fragment, derivative, or variant of a gene product would not necessarily retain the function of the gene product. Accordingly, the specification does not provide adequate description or a representative number of species by which a skilled artisan would recognize that the Applicant had possession of the claimed genera of fragments, variants, or derivative of coding regions.
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 1-3, 10, 12-13, and 18-26 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to a natural product without significantly more. The claims recite a nucleic acid comprising a coding region, an upstream translation control element, and a plurality of downstream translation control elements. This judicial exception is not integrated into a practical application because the nucleic acid is not markedly different from a naturally occurring counterpart, a eukaryotic gene. The claims do not include additional elements sufficient to amount to significantly more than the judicial exception because there are no additional elements that distinguish the nucleic acid from its naturally occurring counterpart.
Roos (D. Roos and M. de Boer, Biochem Biophys Act Mol Basis Dis, May 2021, cited previously in PTO-892 filed 19 May 2026) teaches elements comprising a eukaryotic gene.
Regarding claims 1 and 2, as previously noted in the Requirement for Restriction filed 19 May 2026, the specification only provides a non-limiting definition for what the inventor regards as a "translation control element". The specification states that "'translation control/regulation sequence' or 'translation control/regulation element' may be used to indicate nucleic acid sequences regulating or controlling the translational processes of the nucleic acid molecules of transcripts to the proteins or peptides" (par. 66). Therefore, under the broadest reasonable interpretation, "translation control element" is taken to mean any sequence motif within the nucleic sequence or modification to the nucleic acid that affects translation of the recited nucleic acid or any other nucleic acid in any way. Under this interpretation, each element of the nucleic acid of claim 1 is found in a eukaryotic gene or mRNA transcripts thereof. As noted by Roos, mRNA transcripts in eukaryotes comprise a coding region and are modified at the 5' (upstream) and 3' (downstream) ends flanking the coding region (p. 5 § 2.1). The 5' end of an mRNA is capped by a methylated guanosine "to recognize the first intron for its excision, to promote nuclear export of the mature mRNA to the cytoplasm, to recognize the start codon for translation into protein for promotion of translation" (upstream translation control element) (Roos p. 5 § 2.1). The 3' end of an mRNA coding region comprises a plurality of downstream translation control elements including a termination codon, a polyadenylation signal, a polyadenosine (poly-A) tail, and a 3' untranslated region (3' UTR) (plural downstream translation control elements, claim 1, first and second downstream translation control elements each located downstream of the coding region, claim 2) (Roos p. 5 § 2.1).
Regarding claims 3 and 18, each of the recited genes, human troponin T1 slow skeletal type (TNNT1, NCBI Gene ID 7138), human albumin (ALB, NCBI Gene ID 213), human ferritin light chain (FTL, NCBI Gene ID 2512), human C-C motif chemokine ligand (CCL19, NCBI Gene ID 6363), human angio-associated migratory cell protein (AAMP, NCBI Gene ID 14), human ribosomal protein S27 (RPS27, NCBI Gene ID 6232), and human defensin alpha 5 (DEFA5, NCBI Gene ID 1670), is found naturally occurring in humans. Human protein coding genes comprise the elements recited in claim 1 as taught by Roos; therefore, each of the genes recited in claim 3 and their corresponding mRNA transcripts comprises a plurality of downstream translation control elements (claim 3) and upstream translation control elements (claim 18) derived from one the recited genes or a transcript sequence thereof.
Regarding claims 10 and 12-13, the claims encompass a nucleic acid in which the first, second, and third downstream control elements are derived from RPS27. Therefore, the claims encompass the mRNA encoding RPS27.
Regarding claim 19, each of the claimed sequence identifiers is 100% identical to a region in at least one naturally occurring human transcript variant of the genes TNNT1 ALB, FTL, CCL19, AAMP, RPS27, and DEFA5 (see Alignments 1-7 below). Therefore, each of the mRNA transcripts of the genes TNNT1 ALB, FTL, CCL19, AAMP, RPS27, and DEFA5 comprises one of the upstream control elements set forth in the sequence identifiers recited in claim 19.
Alignment 1: query SEQ ID NO: 1
PNG
media_image1.png
203
786
media_image1.png
Greyscale
Alignment 2: query SEQ ID NO: 2
PNG
media_image2.png
205
780
media_image2.png
Greyscale
Alignment 3: query SEQ ID NO: 3
PNG
media_image3.png
379
778
media_image3.png
Greyscale
Alignment 4: query SEQ ID NO: 4
PNG
media_image4.png
334
778
media_image4.png
Greyscale
Alignment 5: query SEQ ID NO: 5
PNG
media_image5.png
208
786
media_image5.png
Greyscale
Alignment 6: query SEQ ID NO: 6
PNG
media_image6.png
213
779
media_image6.png
Greyscale
Alignment 7: query SEQ ID NO: 7
PNG
media_image7.png
209
786
media_image7.png
Greyscale
Regarding claim 20, eukaryotic genes are transcribed into mRNA (Roos p. 5 § 2.1).
Regarding claim 21, eukaryotic genes comprise, inter alia, promoters upstream of the coding region where transcription factors bind to regulate transcription initiation, sites for RNA polymerases to bind to carry out transcription, an ATG start sequence that serves as the starting site of the coding region, and enhancers located upstream, downstream, or within introns of the gene that regulate transcription initiation (transcription control elements) (Roos pp. 1-2 § 1).
Regarding claim 22, the polyadenylation signal and poly-A tail (polyadenosine sequence) are located downstream of the termination codon (polyadenylation signal sequence or polyadenosine sequence located downstream of the downstream control element) (Roos p. 5 § 2.1).
Regarding claims 23-26, the claims encompass the gene ALB and mRNA transcripts thereof, wherein the coding region encodes for the protein albumin. Minchiotti (L. Minchiotti, et al., Hum Mutat, 2008) teaches that monoclonal antibodies have been created that bind to specific epitopes in albumin (coding region encodes an antigen, claim 24) (p. 1012). Minchiotti further teaches that certain mutations in albumin can result in genetic diseases such as familial dysalbuminemic hypertriiodothyroninemia or familial dysalbuminemic hyperthyroxinemia or result in analbunemia, which causes edema and hyperlipidemia without overt disease (coding region encodes a peptide of a pathogenic antigen, claim 25) (pp. 1011-1012 and Table 1). Such mutations are detectable by genetic sequencing (wherein the coding region encodes at least one marker, claim 23) (Minchiotti p. 1012). Minchiotti further teaches that albumin can act as a carrier for numerous ligands, and this property is frequently exploited to improve distribution of poorly soluble hydrophobic small molecule therapeutics (a peptide for disease treatment, claim 26) (p. 1012).
The Office published the guidance document entitled 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Eligibility Guidance), published 16 Dec 2014. Step 2A was revised to include two prongs (Federal Register / Vol. 84, No. 4 / 07 Jan 2019).
Analysis is as follows:
Step 1: Are the claims drawn to one of the statutory categories of invention (a process, a machine, a manufacture, and/or a composition of matter)?
Step 1: The claim is directed to a composition of matter (a nucleic acid).
Step 1: Yes.
Step 2A, Prong One: Do the claims recite a judicial exception (a law of nature, a natural product/phenomenon, or an abstract idea)?
Step 2A, Prong One: The composition of matter (a nucleic acid) is directed to a natural product. The claim recites a composition that is not markedly different from a eukaryotic gene.
Step 2A, Prong One: Yes.
Step 2A, Prong Two: Do the claims recite additional elements that integrate the judicial exception into practical application of the exception?
Step 2A, Prong Two: This exception is not integrated into practical application because the claims do not recite additional elements that integrate the judicial exception into practical application. As taught by Roos and Minchiotti, every element of the claimed nucleic acid is found naturally occurring eukaryotic genes and transcripts thereof. Therefore, there are no additional elements beyond the judicial exception. See MPEP § 2106.05(h).
Step 2A, Prong Two: No.
Step 2B: Do the claims recite additional elements that individually or in combination amount to significantly more than the judicial exception (i.e., whether the additional elements provide an inventive concept)?
Step 2B: The claims merely recite elements found in a eukaryotic gene and therefore, there are no additional elements that could amount to significantly more.
Step 2B: No.
The markedly different characteristics analysis performed in Step 2A, Prong One is a comparison of the nature-based product limitation to its naturally occurring counterpart in its natural state. Markedly different characteristics can be expressed as the product’s structure, function, and/or other properties. Product of nature exceptions include both naturally occurring products and non-naturally occurring products that lack markedly different characteristics from any naturally occurring counterpart. See MPEP § 2106.04(b)(II). If the claim recites a nature-based product limitation that does not exhibit markedly different characteristics, the claim is directed to a product of nature exception, and the claim will require further analysis to determine eligibility based on whether additional elements add significantly more to the exception. In accordance with this analysis, nucleic acid, for example, is eligible when there is a resultant change in characteristics sufficient to show a marked difference from a eukaryotic gene. It is concluded here that the claimed nucleic acid is not markedly different from its naturally occurring counterpart, a eukaryotic gene, as the claim does not recite structural limitations that distinguish the nucleic acid composition from the composition of a eukaryotic gene.
The Supreme Court has identified several considerations for determining whether a claim with additional elements amounts to significantly more than the judicial exception itself. Limitations that may qualify as significantly more when recited in a claim with a judicial exception include: improvements to another technology or technical field; improvements to the functioning of the computer itself; applying the judicial exception with, or by use of, a particular machine; effecting a transformation or reduction of a particular article to a different state or thing; adding a specific limitation other than what is well-understood, routine and conventional in the field, or adding unconventional steps that confine the claim to a particular useful application; or other meaningful limitations beyond generally linking the use of the judicial exception to a particular technological environment.
Limitations that were found not to be enough to qualify as significantly more when recited in a claim with a judicial exception include: adding the words ‘apply it’ (or an equivalent) with the judicial exception; mere instructions to implement an abstract idea on a computer; simply appending well-understood, routine and conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception; adding insignificant extra-solution activity to the judicial exception; or generally linking the use of the judicial exception to a particular technological environment or field of use.
In the instant case, the limitations of the claims do not impose limits on the scope of the claim such that the nucleic acid is markedly different from a naturally occurring product. Accordingly, based on analysis of the claim as a whole, the claims do not recite additional elements adding significantly more than the judicial exception and are thus rejected under 35 U.S.C. § 101 because the claimed invention is not directed to patent eligible subject matter.
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.
Claims 1-3, 10, 12-13, 18-22, and 26 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Tsui (S.K.W. Tsui, et al., Biochem Mol Biol, 1996) as evidenced by Roos (D. Roos and M. de Boer, Biochem Biophys Act Mol Basis Dis, May 2021, cited previously in PTO-892 filed 19 May 2026).
Regarding claims 1-2, 20 and 22, Tsui discloses the sequence for the human ribosomal protein S27 (RPS27) cDNA, which is generated from the mRNA transcript (nucleic acid, claim 1, mRNA, claim 20 (Abstract).The transcript encodes for RPS27 (the nucleic comprises a coding region, claim 1) (Abstract). As previously noted in the Requirement for Restriction filed 19 May 2026, the specification only provides a non-limiting definition for what the inventor regards as a "translation control element". The specification states that "'translation control/regulation sequence' or 'translation control/regulation element' may be used to indicate nucleic acid sequences regulating or controlling the translational processes of the nucleic acid molecules of transcripts to the proteins or peptides" (par. 66). Therefore, under the broadest reasonable interpretation, "translation control element" is taken to mean any sequence motif within the nucleic sequence or modification to the nucleic acid that affects translation of the recited nucleic acid or any other nucleic acid in any way. The transcript comprises a polyadenylation signal (a first downstream translation control element downstream of the coding region, claims 1-2, polyadenylation signal sequence, claim 22) (Abstract and Results p. 613). Tsui is silent regarding additional translation control elements. However, as evidenced by Roos, mRNA transcripts in eukaryotes comprise a coding region and are modified at the 5' (upstream) and 3' (downstream) ends flanking the coding region (p. 5 § 2.1). The 5' end of an mRNA is capped by a methylated guanosine "to recognize the first intron for its excision, to promote nuclear export of the mature mRNA to the cytoplasm, to recognize the start codon for translation into protein for promotion of translation" and a start codon is located at the 5' end of the coding region (upstream translation control elements) (Roos p. 5 § 2.1). The 3' end of an mRNA coding region comprises a plurality of downstream translation control elements including a stop codon, a polyadenylation signal, a polyadenosine (poly-A) tail, and a 3' untranslated region (3' UTR) (plural downstream translation control elements, claim 1, first and second downstream translation control elements each located downstream of the coding region, claim 2) (Roos p. 5 § 2.1). Therefore, the human RPS27 mRNA transcript disclosed by Tsui inherently comprises upstream and plural downstream translation control elements.
Regarding claims 3, 10, and 18, the naturally occurring human RPS27 transcript comprises upstream translation control elements (a 5' cap and a start codon) located upstream of the coding region and plural downstream translation control elements (a stop codon, a 3'UTR, a polyadenylation signal, and a poly(A) tail) located downstream of the coding region, as evidenced by Roos; therefore, Tsui inherently discloses a nucleic acid in which each of the plural downstream translation control elements is derived from RPS27 (claims 3 and 10) and in which the upstream translation control element is derived from RPS27 (claim 18).
Regarding claims 12-13, Tsui discloses that the RPS27 mRNA transcript comprises a polyadenylation signal (a first downstream translation control element). Roos notes that all eukaryotic genes comprise a stop codon, a polyadenosine (poly-A) tail, and a 3' untranslated region (3' UTR) downstream of the coding region (second, third, and fourth downstream translation control elements). Therefore, Tsui inherently discloses a nucleic acid RPS27 comprising a first, a second, and a third downstream translation control element derived from human RPS27.
Regarding claim 19, the sequence set forth in SEQ ID NO: 6 is 100% identical to a region in the human transcript of RPS27 (see Alignment 6 in the rejection of claim 19 under 35 U.S.C. § 101 above). Therefore, Tsui inherently discloses the upstream translation control element sequence set forth in SEQ ID NO: 6.
Regarding claim 21, Tsui discloses that RPS27 is expressed as a protein in humans; therefore, Tsui inherently discloses a transcription control element in RPS27 (Introduction p. 611).
Regarding claim 27, Tsui discloses a bacteriophage comprising the cDNA encoding RPS27 (recombinant expression vector into which the nucleic acid is inserted) (Methods p. 612).
Claims 1-3, 12-13, 18, and 20-27 are rejected under 35 U.S.C. § 102(a)(1) as being anticipated by Asrani (K.H. Asrani, et al., RNA Biol, 2018) as evidenced by Roos (D. Roos and M. de Boer, Biochem Biophys Act Mol Basis Dis, May 2021, cited previously in PTO-892 filed 19 May 2026).
Regarding claims 1 and 20, Asrani discloses mRNA (nucleic acid molecules, claim 1 and RNA, claim 20) comprising a coding region that encodes for the arginase 1 (ARG-1) and various embodiments of combinations of 5' untranslated regions (5'UTR, upstream translation control element located upstream of the coding region) and 3'UTR (Abstract, Introduction p. 756, and Table 2). Each of the mRNA comprise three in-frame stop codons, a 3'UTR, and a 100-nucleotide poly-A repeat downstream of the coding region (plural downstream translation control elements located downstream of the coding region) (Introduction p. 756, Table 2, and Methods p. 760).
Regarding claim 2, each of the mRNA disclosed by Asrani comprise three in-frame stop codons (a first downstream translation control element), a 3'UTR (a second downstream translation control element), and a 100-nucleotide polyadenosine poly-A repeat downstream of the coding region (Introduction p. 756, Table 2, and Methods p. 760).
Regarding claims 3 and 12-13, in some embodiments disclosed by Asrani, the 3'UTR is derived from the human albumin gene (ALB, NCBI Gene ID 213) (Tables 1 and 2). Each of the mRNA comprise three in-frame stop codons (a first downstream translation control element), a 3'UTR (a second downstream translation control element), and a 100-nucleotide poly-A repeat downstream of the coding region (a third downstream translation control element) (Introduction p. 756, Table 2, and Methods p. 760). As noted by Roos, all eukaryotic mRNA transcripts comprise a stop codon, a 3'UTR, and a poly-A tail downstream of the coding region; therefore, each of the downstream control elements is derived from human ALB (Roos p. 5 § 2.1).
Regarding claim 18, in some embodiments disclosed by Asrani, the 5'UTR is derived from ALB (upstream translation control element) (Tables 1 and 2).
Regarding claim 21, transcription of the mRNA disclosed by Asrani was driven by a T7 RNA polymerase by binding to a T7 RNA polymerase promoter (transcription control element operably linked to the coding region) (Methods p. 760).
Regarding claim 22, the mRNA disclosed by Asrani comprise a 100-nucleotide poly-A repeat downstream of the 3'UTR (polyadenosine sequence located downstream of the downstream translation control element) (Discussion p. 760).
Regarding claim 23, Asrani discloses measurement of arginase I expression from mRNA constructs with different 3'UTR and 5'UTR combination to assess translation efficiency (wherein the coding region encodes at least one reporter protein) (Results p. 757, Fig. 1, and Table 2).
Regarding claims 24-26, Asrani discloses measurement of ARG1 protein levels from cells transfected with the mRNA constructs using an ARG1-specific primary antibody (wherein the coding region encodes an antigen, claim 24) (Methods p. 761). Regarding claim 25, note that a limiting definition for a pathogenic antigen is not provided in the specification. Therefore, under the broadest reasonable interpretation, a pathogenic antigen is construed to encompass any molecule that can bind to an antibody or T-cell receptor and is associated with a disease or pathological process. Asrani notes that ARG1 deficiency is a rare genetic disease and that exogenous expression of the ARG1 protein has a putative clinical benefit (Introduction p. 756). Therefore, the mRNA constructs encoding for ARG1 disclosed by Asrani inherently disclose a coding region that encodes for an antigen associated with a disease (pathogenic antigen, claim 25) and a peptide for disease treatment (claim 26).
Regarding claim 27, Asrani discloses cloning the mRNA constructs into plasmids used to transfect cells in culture (a recombinant expression vector into which the nucleic acid is inserted) (Methods pp. 760-761).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 12-13, and 18-27 of this application are patentably indistinct from claim 1, 12-13, and 24 of Application No. 18/291,589. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claims 1-3, 12-13, and 18-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12-13, and 24 of copending Application No. 18/291,589 (reference application, hereafter '589) as evidenced by Kwak (J.E. Kwak, et al., Nat Commun, 2019). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are anticipated by claims 1, 12-13, and 24 of '589. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, claim 1 of '589, from which claim 12 of '589 depends, recites a nucleic acid molecule comprising a coding region and a translation control element that are operably linked and wherein the translation control element comprises a first translation control element located upstream of the coding region (an upstream translation control element) and a second translation control element located downstream of the coding region (a downstream translation control element). Claim 12 of '589 further recites that the nucleic comprises a polyadenylation signal sequence or a polyadenoside sequence (plural downstream translation control elements).
Regarding claims 2 and 22, claim 1 of '589 recites that the downstream translation control element comprises the sequence set forth in SEQ ID NO: 1 (first downstream translation control element) and claim 12 further recites polyadenylation signal sequence or a polyadenoside sequence (second and third downstream translation control element).
Regarding claims 3 and 12-13, claim 1 of '589 recites that the translation control element is derived from troponin T1 (TNNT1). By convention in the art, capitalization of a gene name signifies a human gene. Therefore, each of the plural downstream translation control elements that are part of the overall translation control element is derived from human TNNT1.
Regarding claims 18-20, claim 1 of '589 recites that the first (upstream) translation control element comprises the sequence set forth in SEQ ID NO. 1, which is 100% identical to SEQ ID NO: 1 of the immediate application. As discussed above in the rejection of claim 19 under 35 U.S.C. § 101, SEQ ID NO: 1 of the immediate application is 100% identical to a region in mRNA transcripts of human troponin T1 (TNNT1) (wherein the nucleic acid is mRNA, claim 20). Therefore, the upstream translation control element is derived from human TNNT1 (claim 18).
Alignment 15
Qy: Application 18/719,347 SEQ ID NO: 1
DB: Application 18/291,589 SEQ ID NO: 1
PNG
media_image8.png
141
613
media_image8.png
Greyscale
Regarding claim 21, claim 12 of '589 recite a transcription control element operatively linked to the coding region.
Regarding claims 23-26, claim 1 of '589 recites that the coding region encodes for an immunogen of severe fever with thrombocytopenia syndrome virus (SFTSV). As evidenced by Kwak, an SFTSV antigen (claim 24) can be delivered to a patient to elicit an immune response as a vaccination (immunogen) (Abstract and Fig. 1a). SFSTV is infectious, therefore the SFSTV antigen is a pathogenic antigen (claim 25) (Abstract). Delivery of an SFSTV antigen can elicit an immune response to prevent infection upon subsequent exposure to the virus (peptide for disease treatment, claim 26) (Abstract). Therefore, the coding region encoding an SFSTV antigen inherently anticipates claims 23-26.
Regarding claim 27, claim 24 of '589, which depends from claim 13 of '589, recites a recombinant expression vector comprising a nucleic acid comprising all of the same elements of the nucleic acid claim 12 of '589 (recombinant expression vector into which the nucleic acid is inserted).
Claims 1-2 and 21 of this application are patentably indistinct from claim 5 of Application No. 19/019,850. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claims 1-2 and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 19/019,850 (reference application, hereafter '850). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are anticipated by claim 5 of '850. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 5 of '850, which depends from claims 1-4 of '850, is drawn to a nucleic acid molecule comprising a coding region (claim 1) operably linked to an expression control element comprising a transcription control element (claim 21) and a translation control element comprising an upstream translation control element located upstream of the coding region and a downstream translation control element located downstream of the coding region (claim 1), which comprises a first and a second downstream translation control element (plural downstream translation control elements, claims 1-2).
Allowable Subject Matter
Claim 4 is free of the prior art.
The nearest prior art to the subject matter in claim 4 is Thess (US 10,080,809 B2, 2018). Thess teaches artificial nucleic acids comprising at least one 5'UTR (an upstream translation control element), at least one open reading frame (ORF, a coding region), and least one 3'UTR (downstream translation control element) (Abstract). Thess further teaches including multiple heterologous 3'UTR derived from 3'UTR of human genes in different combinations to improve mRNA stability and translation efficiency (col. 3 line 42 – col. 4 line16, col. 27 lines 15-21, and col. 28 line 34 – col. 29 line 17). In particular, Thess teaches that such 3'UTR can be chosen from 3'UTR derived from a group of genes including human albumin gene (ALB), or fragments thereof exemplified in SEQ ID NO: 1369 and SEQ ID NO: 1376 – SEQ ID NO: 1392. (col. 30 line 34 – col. 31 line 15 and col. 62 line 57 – col. 63 line 23). Thess does not teach combinations of 3'UTR derived from TNNT1, FTL, CCL19, AAMP, RPS27, or DEFA5 (sequences of which are set forth in SEQ ID NO: 8 and 10-14, respectively). However, the most similar ALB 3'UTR sequence contemplated by Thess (SEQ ID NO: 1369) is only 98.9% identical to SEQ ID NO: 9 of the present application. Thess teaches methods to optimize combinations of heterologous 5'UTR and 3'UTR (col. 28 line 34 – col. 29 line 17), but neither Thess nor the art provide sufficient contemplation for a skilled artisan to optimize the sequence of the 3'UTR itself, especially for mRNA comprising multiple 3'UTR with repeats of the same 3'UTR or combinations of heterologous 3'UTR, to arrive at the claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric B Wright whose telephone number is (571) 272-2607. The examiner can normally be reached Mo - Fr, 09:00 a.m. - 05:00 p.m. Eastern. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant may use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/ Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights