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
This action is written in response to applicant’s correspondence received 12/10/2025. Claims 57, 70-71, 74, and 77 are cancelled. Claims 52-56, 58-69, 72-72, 75-76, and 78-81 are currently pending. Claim 80 is withdrawn from prosecution as being drawn to non-elected subject matter.
The restriction requirement mailed 06/04/2025 is still deemed proper. Applicant's election with traverse of Group I, claims 52-79 and 81, directed to an engineered DNA molecule capable of being replicated in a cell, in the reply filed on 8/1/2025 is acknowledged. Claim 80 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 8/1/2025. Therefore, claims 52-56, 58-69, 72-72, 75-76, 78-79, and 81 are under examination.
Any rejection or objection not reiterated herein has been overcome by amendment. Applicant’s amendments and arguments have been thoroughly reviewed, but are not persuasive to place the claims in condition for allowance for the reasons that follow.
Examiner’s Note
Claims 57 and 63 should have been included in the NSDP rejections mailed in the Non-Final Office Action mailed 9/23/2025. Therefore, a 2nd Non-Final has been issued, despite the amendments to cancel claim 57 and incorporate the limitations into independent claim 52 and to amend claim 63 to be rewritten in independent form for the reasons that follow.
Nucleotide and/or Amino Acid Sequence Disclosures – compliant
Applicant’s arguments that SEQ ID NOs: 15-17 in claim 58 are fewer than 10 nucleotides in length and not required to be listed in the Sequence Listing is persuasive. Therefore, the sequence disclosures are compliant.
Drawings - withdrawn
The objection to drawings in withdrawn in view of Applicant’s amended drawings filed 12/10/2025.
Specification - withdrawn
The objection to the specification for using trade names or marks without proper symbols in withdrawn in view of Applicant’s amendment filed 12/10/2025.
Claim Objections – new necessitated by amendment
Claims 58 and 60 are objected to because of the following informalities:
Claim 58 recites the phrases “(SEQ ID NO: 15)” and “(SEQ ID NO: 16)”, which have blank listings in the sequence listing. The Office suggests deleting the listed phrases, while keeping the nucleotide sequences themselves.
Claim 60, depending from amended claim 52, recites the limitation “when the element c and the element d exist simultaneously”. Amended claim 52 now requires both elements c and d, therefore this phrase in claim 60 is unnecessary and confusing.
Appropriate correction is required.
Claim Rejections - 35 USC § 101 - withdrawn
Rejection of claim 73 is withdrawn in view of Applicant’s amendment to add that the cell is prokaryotic (and no longer reads on a human organism).
Claim Rejections - 35 USC § 112 - withdrawn
Rejection of claims 67-68 and 70-71 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is withdrawn in view of Applicant’s amendment to cancel claims 70-71 and to change the dependency from claim 52 to claim 65 to correct insufficient antecedent basis.
Rejection of claims 75-77 and 79 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn in view of Applicant’s amendment to claim 75 to include the limitations of claim 52, to cancel claim 77, and to change the dependency of claim 79 from claim 52 to claim 75.
Claim Rejections - 35 USC § 102 – withdrawn
Rejection of claims 52-56, 58-59, 61, 65-71, and 73-79 under 35 U.S.C. 102(a)(1) as being anticipated by Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025) is withdrawn in view of Applicant’s amendment to incorporate the limitations of 57 into independent claim 52 and to cancel claims 57, 70-71, 74, and 77.
Claim Rejections - 35 USC § 103 – withdrawn
Rejection of claim 72 under 35 U.S.C. 103 as being unpatentable over Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025) as applied to claims 52-56, 58-59, 61, 65-71, and 73-79 above, and further in view of Yu et al. (US20230310655A1; published 10/05/2023 with priority to 12/23/2019) is withdrawn in view of Applicant’s amendment to delete SEQ ID NO: 22.
Rejection of claim 72 under 35 U.S.C. 103 as being unpatentable over Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025) as applied to claims 52-56, 58-59, 61, 65-71, and 73-79 above, and further in view of Jin et al. (US20170304385A1; published 10/26/2017) is withdrawn in view of Applicant’s amendment to incorporate the limitations of 57 into independent claim 52.
Rejection of claim 81 under 35 U.S.C. 103 as being unpatentable over Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025) as applied to claims 52-56, 58-59, 61, 65-71, and 73-79 above, and further in view of Liu et al. (DNA/RNA hybrid primer mediated poly (A) tag library construction for Illumina sequencing. Polyadenylation in Plants: Methods and Protocols. Springer New York. 175-184; published 2014) in view of Applicant’s amendment to incorporate the limitations of 57 into independent claim 52.
Double Patenting – new rejections
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 52-56, 58-69, 73, 75-76, 78-79, and 81 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12318441 (corresponding to Application number 18/770,056) in view of Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025), Liu et al. (DNA/RNA hybrid primer mediated poly (A) tag library construction for Illumina sequencing. Polyadenylation in Plants: Methods and Protocols. Springer New York. 175-184; published 2014), and Jin et al. (US20170304385A1; published 10/26/2017).
Claims 1-25 of the ‘441 patent encompass polynucleotide molecules encoding HPV E6, E7, and E2 antigen fusion proteins and comprising poly(A) tails of 101-200 nucleotides long ending in an A or non-A nucleotide and that element d consists of GATATC (SEQ ID NO: 15), which is palindromic (claims 52-54, 58, 62-63, and 75). Claim 13 of the ‘441 patent encompasses SEQ ID NO: 27 with 100% sequence identity to instant claim 64’s SEQ ID NO: 3 (claim 64; see Office Appendix for sequence alignment in OA mailed 9/23/2025), which encodes a 123 nucleotide poly(A) tail with a configuration of 60A-element d-19A-G-19A-G-17A (claims 52-56 and 62-63). Claim 13 of the ‘441 patent further teach the poly(A) tail structure element a-element d-element b-element c-element b-element c-element b (claim 62). Accordingly, claim 13 of the ‘441 patent teaches that the element c is G (claim 56), that the number of element d is 1-5 (claim 59), wherein when element c and element d exist simultaneously and the total number of element c and element d is 2-15 (claim 60), and the 3’ portion of the poly(A) tail comprises one or more non-A nucleotides (claim 61). Claims 1-25 of the ‘441 patent teach DNA molecules comprising a replicon, an antibiotic resistance gene, a promoter, a 5' UTR coding sequence, a protein coding sequence, and a 3' UTR coding sequence (claims 65-69). Claims 21-25 of the ‘441 patent teach a method of delivering the DNA molecule to an individual, and therefore, teach a cell comprising the DNA molecule (partial claim 73). Claim 12 of the ‘441 patent teaches uridines in the mRNA molecule are chemically modified uridines (claim 76).
Claim 1-25 of the ‘441 patent do not teach that the cell comprising the DNA molecule is a prokaryotic E. coli cell (claim 73) and a library comprising the DNA molecule, the RNA molecule, and DNA/RNA hybrid molecules (claims 78-79 and 81).
Eberle’s disclosure is directed to the stabilization of poly(a) sequence encoding DNA sequences (entire document). Eberle teaches the DNA sequence encoding the 3′ poly(A) sequence (3′ poly(A) cassette), i.e. a stretch of consecutive dA:dT base pairs, is subjected to shortening in some bacterial subclones, when propagated in E. coli. Eberle teaches nucleic acid molecules containing poly (dA:dT) regions which contain at least one disruption by a sequence not encoding a sequence solely composed of A residues (abstract).
Regarding claim 73, Eberle teaches a cell comprising the DNA molecule and that the cell is a prokaryotic E. coli cell (paras 0010-0016, 0049-0053, 0077-0078, and 0120; and Examples 1-2).
Regarding claim 78, Eberle teaches 10 different poly(A) tail constructs (Examples 2 and 6). The instant specification, on page 28, defines a library comprising DNA molecules as comprising “at least two DNA molecules with different poly(A) tail coding sequences. Therefore, Eberle teaches a library comprising DNA molecules of the invention.
Regarding claim 79, Eberle teaches at least 2 RNA molecules encoded by DNA constructs (Examples 2 and 4-6; and paras 0185-0186). The instant specification, on page 31, defines a library comprising mRNA molecules as comprising “at least two mRNA molecules having different poly(A) tail coding sequences. Therefore, Eberle teaches a library comprising an RNA molecule encoded by the engineered DNA molecules.
Liu’s disclosure is directed to DNA/RNA hybrids to generate poly(A) tags libraries (see entire document). Liu teaches the importance of alternative polyadenylation of mRNA in the regulation of gene expression in eukaryotes (see Introduction).
Regarding claim 81, Liu teaches methods of generating poly(A) tag libraries comprising DNA/RNA hybrids (pp. 175-179).
It would have been obvious to one of ordinary skill in the art to have modified the products and methods of the ‘441 patent with the prokaryotic E. coli cell as taught by Eberle to amplify the engineered nucleic acid molecules and further to create DNA/RNA hybrid libraries of poly(A) sequences as taught by Liu. Eberle teaches DNA and RNA molecules having specific poly(A) tail structures engineered for stability and regulation of expression. Liu teaches construction of a poly(A) tag library using DNA/RNA hybrid molecules. One would have had a reasonable expectation of success of combing the prior art elements because Eberle and Liu are directed to engineered nucleic acid molecules comprising poly(A) tails. The 441’ patent, Eberle, and Liu further teach engineered nucleic acid molecules comprising poly(A) tails. Thus, the claimed invention as a whole is prima facie obvious.
Claim 72 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 12318441 (corresponding to Application number 18/770,056) in view of Jin et al. (US20170304385A1; published 10/26/2017).
The teachings of the ‘441 patent are discussed in the NSDP rejection above and are applied to claim 72 as they have been applied to claims 52-56, 58-69, 73, 75-76, 78-79, and 81.
However, the ‘441 patent does not specifically teach a polynucleotide sequence encoding the HPV E6/E7 represented by SEQ ID NO: 23.
Jin’s disclosure is directed to methods for improving cervical cancer treatment
caused by HPV infection using polynucleotide encoding an HPV E6/E7 fusion protein (entire document).
Regarding claim 72, Jin teaches HPV E6/E7 fusion constructs for therapeutic
vaccine (Example 1 and paras 0439-0456). Jin teaches a plasmid encoding a fusion HPV E6/E7 protein with the sequence of SEQ ID NO: 15 having 99.2% sequence
identity to Applicant’s claimed SEQ ID NO: 23 (see Office Appendix for sequence
alignment in OA mailed 9/23/2025).
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to have modified the Eberle’s engineered DNA molecules encoding HPV E6 and E7 protein with Jin’s fusion HPV E6/E7 protein sequence because it would have amounted to a simple substitution of known HPV protein sequences to obtain predictable results. One could have substituted Jin’s fusion HPV E6/E7 protein sequence for Eberle’s and would have had a reasonable expectation of success because the ‘441 patent and Jin teach HPV protein sequences and are directed to engineered nucleic acid molecules and their expression. Thus, the claimed invention as a whole is prima facie obvious.
Claims 52-56, 58-69, 73, 75-76, 78-79, and 81 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19089584 in view of Eberle et al. (US20170166905A1; published 06/15/2017; cited in the IDS filed 03/19/2025), Liu et al. (DNA/RNA hybrid primer mediated poly (A) tag library construction for Illumina sequencing. Polyadenylation in Plants: Methods and Protocols. Springer New York. 175-184; published 2014).
Claims 1-20 of the ‘584 application encompass polynucleotide molecules encoding HPV E6, E7, and E2 antigen fusion proteins and comprising poly(A) tails of 101-200 nucleotides long ending in an A or non-A nucleotide and that element d consists of GATATC (SEQ ID NO: 15), which is palindromic (claims 52-54, 58, 62-63, and 75). Claim 10 of the ‘584 application encompasses SEQ ID NO: 27 with 100% sequence identity to instant claim 64’s SEQ ID NO: 3 (claim 64; see Office Appendix for sequence alignment in OA mailed 9/23/2025), which encodes a 123 nucleotide poly(A) tail with a configuration of 60A-element d-19A-G-19A-G-17A (claims 52-56 and 62-63). Claim 10 of the ‘584 application further teach the poly(A) tail structure element a-element d-element b-element c-element b-element c-element b (claim 62). Accordingly, claim 10 of the ‘584 application teaches that the element c is G (claim 56), where element d consists of GATATC (SEQ ID NO: 15) (claim 58), that the number of element d is 0-5 (claim 59), wherein when element c and element d exist simultaneously and the total number of element c and element d is 2-15 (claim 60), and the 3’ portion of the poly(A) tail comprises one or more non-A nucleotides (claim 61). Claims 1-20 of the ‘584 application teach DNA molecules comprising a replicon, an antibiotic resistance gene, a promoter, a 5' UTR coding sequence, a protein coding sequence, and a 3' UTR coding sequence (claims 65-69). Claims 17-20 of the ‘584 application teach a method of delivering the DNA molecule to an individual, and therefore, teach a cell comprising the DNA molecule (partial claim 73). Claim 9 of the ‘584 application teaches uridines in the mRNA molecule are chemically modified uridines (claim 76).
Claim 1-20 of the ‘584 application do not teach that the cell comprising the DNA molecule is a prokaryotic E. coli cell (claim 73) and a library comprising the DNA molecule, the RNA molecule, and DNA/RNA hybrid molecules (claims 78-79 and 81).
Eberle’s disclosure is directed to the stabilization of poly(a) sequence encoding DNA sequences (entire document). Eberle teaches the DNA sequence encoding the 3′ poly(A) sequence (3′ poly(A) cassette), i.e. a stretch of consecutive dA:dT base pairs, is subjected to shortening in some bacterial subclones, when propagated in E. coli. Eberle teaches nucleic acid molecules containing poly (dA:dT) regions which contain at least one disruption by a sequence not encoding a sequence solely composed of A residues (abstract).
Regarding claim 73, Eberle teaches a cell comprising the DNA molecule and that the cell is a prokaryotic E. coli cell (paras 0010-0016, 0049-0053, 0077-0078, and 0120; and Examples 1-2).
Regarding claim 78, Eberle teaches 10 different poly(A) tail constructs (Examples 2 and 6). The instant specification, on page 28, defines a library comprising DNA molecules as comprising “at least two DNA molecules with different poly(A) tail coding sequences. Therefore, Eberle teaches a library comprising DNA molecules of the invention.
Regarding claim 79, Eberle teaches at least 2 RNA molecules encoded by DNA constructs (Examples 2 and 4-6; and paras 0185-0186). The instant specification, on page 31, defines a library comprising mRNA molecules as comprising “at least two mRNA molecules having different poly(A) tail coding sequences. Therefore, Eberle teaches a library comprising an RNA molecule encoded by the engineered DNA molecules.
Liu’s disclosure is directed to DNA/RNA hybrids to generate poly(A) tags libraries (see entire document). Liu teaches the importance of alternative polyadenylation of mRNA in the regulation of gene expression in eukaryotes (see Introduction).
Regarding claim 81, Liu teaches methods of generating poly(A) tag libraries comprising DNA/RNA hybrids (pp. 175-179).
It would have been obvious to one of ordinary skill in the art to have modified the products and methods of the ‘584 application with the prokaryotic E. coli cell as taught by Eberle to amplify the engineered nucleic acid molecules and further to create DNA/RNA hybrid libraries of poly(A) sequences as taught by Liu. Eberle teaches DNA and RNA molecules having specific poly(A) tail structures engineered for stability and regulation of expression. Liu teaches construction of a poly(A) tag library using DNA/RNA hybrid molecules. One would have had a reasonable expectation of success of combing the prior art elements because Eberle and Liu are directed to engineered nucleic acid molecules comprising poly(A) tails. The ‘584 application, Eberle, and Liu further teach engineered nucleic acid molecules comprising poly(A) tails. Thus, the claimed invention as a whole is prima facie obvious.
Claim 72 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of copending Application No. 19089584 in view of in view of Jin et al. (US20170304385A1; published 10/26/2017).
The teachings of the ‘584 application are discussed in the NSDP rejection above and are applied to claim 72 as they have been applied to claims 52-56, 58-69, 73, 75-76, 78-79, and 81.
However, the ‘584 application does not specifically teach a polynucleotide sequence encoding the HPV E6/E7 represented by SEQ ID NO: 23.
Jin’s disclosure is directed to methods for improving cervical cancer treatment
caused by HPV infection using polynucleotide encoding an HPV E6/E7 fusion protein (entire document).
Regarding claim 72, Jin teaches HPV E6/E7 fusion constructs for therapeutic
vaccine (Example 1 and paras 0439-0456). Jin teaches a plasmid encoding a fusion HPV E6/E7 protein with the sequence of SEQ ID NO: 15 having 99.2% sequence
identity to Applicant’s claimed SEQ ID NO: 23 (see Office Appendix for sequence
alignment in OA mailed 9/23/2025).
It would have been obvious to one of ordinary skill in the art before the effective
filing date of the claimed invention to have modified the Eberle’s engineered DNA molecules encoding HPV E6 and E7 protein with Jin’s fusion HPV E6/E7 protein sequence because it would have amounted to a simple substitution of known HPV protein sequences to obtain predictable results. One could have substituted Jin’s fusion HPV E6/E7 protein sequence for Eberle’s and would have had a reasonable expectation of success because the ‘584 application and Jin teach HPV protein sequences and are directed to engineered nucleic acid molecules and their expression. Thus, the claimed invention as a whole is prima facie obvious.
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive. Applicant argues that claim 57 was indicated to be allowable if rewritten independent form including all of the limitations of the base claim and any intervening claims and that claim 52 is amended to recite the features of former claim 57.
In response, the Office apologizes for the confusion. Cancelled claim 57 recited that element d comprises a palindromic sequence. The ‘441 patent and the ‘584 application teach SEQ ID NO: 27, which comprises the palindromic sequences of element d taught in claims 58 and 64. Accordingly, new NSDP rejections have been issued.
Applicant further argues that although both SEQ ID NO: 23 and SEQ ID NO: 24 relate to HPV protein encoding sequences, the encoding sequence of the HPV in SEQ ID NO: 23 and SEQ ID NO: 24 are not the same as those in either the '441 patent or the '584 application.
This argument is moot because claim 72 is rejected over the '441 patent and the '584 application in view of Jin, as detailed in the obviousness NSDP rejections above.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KHALEDA B HASAN whose telephone number is (571)272-0239. The examiner can normally be reached IFP, Monday - Friday 7:30am-5pm.
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/KHALEDA B HASAN/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636