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 .
Election/Restrictions
Applicant’s election of group I (claims 1-16, 19, 22, 26-28, 30, 33-35, 37, 39, 41-42, 56, and 59-60) and species SEQ ID NO: 50 (claim 39) in the reply filed on 7/23/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Upon further consideration, the non-elected sequences in claim 39 are rejoined with the elected species and examined.
No claims are withdrawn at this time because the claims directed to a non-elected invention were cancelled in the amendment filed on 7/23/25.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," 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 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) 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") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) 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 of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Also, nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). For example, see pages 8 and 9. Please review the entire specification and drawings for any other sequences that do no comply with sequence rules.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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.
Drawings
The drawings are objected to because the view numbers for Figures 1-4, 6, 7, 10, 11, 13, 14, 15, 16, 17, 18, 19, and 23 are preceded by the word “Figure” instead of the abbreviation “FIG.”. See 37 1.84(u)(1) states, “View numbers must be preceded by the abbreviation “FIG.”.
In addition, the description of drawings refer to color drawings but the drawings appear to be in black and white. See page 3 (Figure 3A and 3C) of the specification. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Specification
The disclosure is objected to because of the following informalities: the specification refers to color drawings, however, there are no color drawings of record. For example, see page 3 of the specification. Please review the specification for any other description of color drawings.
Appropriate correction is required.
Claim Objections
Claims 22 and 39 are objected to because of the following informalities: The claims have a period and a semi-colon after the term “SEQ ID NO.:”. Suggest removing either the period or semi-colon. Appropriate correction is required.
Claim Interpretation and State of the Art
Claim 34 recites a G-rich region comprising 4 MAZ sequences. The specification contemplates the term, but does not describe what the abbreviation stand for or what is a MAZ nucleotide sequence (pages 26-27). Pages 26-27 studied a G quad sequence and discussed MAZ. A search of the prior art indicates that a MAZ sequence is 60 bp long and a powerful transcription blocker (Ashfield EMBO 13: 5656-67, 1994). It appears that the MAZ sequence was taught by Ashfield and is a G quad sequence. If this interpretation is incorrect, than Applicant can provide an explanation for the term and whether it is directed to a well-known zinc finger protein or a G quad sequence.
In addition, ligand-binding aptamers and method of making the aptamers are well known in the prior art. For example, see Kelvin, RNA Biology 2023, 20, 457-468 (cited on an IDS) and Takoh (US 201301572729).
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 37 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 37 embraces a nucleic acid sequence comprising a poly A aptamer comprising an engineered intron having a triplet sequence that modulates (increases or decreases) the strength of intron splicing. The specification contemplates that the sequence can be any three nucleotides and lists several sequences (paragraph 52). The instant claim and specification recite the limitation and potential nucleic acid triplet sequences, but do not describe any triplet sequence that has the desired biological activity (modulates strength of the intron splicing). As shown in paragraph 52 of the as-filed specification, there is a variation amongst species of triplet sequences. Kay et al. (US 20130210897, cited on an IDS) teach that an intron can be an intronic cassette comprising an intron and one or more sequences including splice donor sequence, splice acceptor sequence, G triplet sequence, pyrimidine rich tract, consensus point sequence that promote out-splicing of the intron (paragraph 35). Thus, one of skill in the art could envision one species, G triplet sequence that can promote out-splicing of the intron. See Hybritech Inc. v. Monoclonal Antibodies, Inc., 802 F.2d at 1384, 231 USPQ at 94. See also Capon v. Eshhar, 418 F.3d 1349, 1357, 76 USPQ2d 1078, 1085 (Fed. Cir. 2005) cited in MPEP 2163. However, this does not provide written support for the genus of triplet sequences having the desired biological activity. The skilled artisan would have to experiment with any other triplet sequence and determine if it modulates the strength of the intron splicing.
Thus, claim 37 does not have written description.
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 19 and 33-34 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.
Claim 19 recites the limitation "double stranded RNA stem between binding pocket of the third aptamer and the three way junction" in line 2.
Claim 33 recites the limitation "the expressible polypeptide and 3’ of the G-U rich region" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 34 is also rejected because it depends on claim 33.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 41-42 and 59-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kay et al. (US 20130210897, cited on an IDS).
The limitation “for delivery of the system(nucleic acid) of claim 1(56)” does not require the system(nucleic acid) in claim 1 or 56 because the limitation is an intended use of the vector and does not require the instant system or instant nucleic acid. Thus, the broadest reasonable interpretation of the claimed product embraces any vector (viral vector). ‘897 teaches an AAV vector (page 3).
Claims 41-42 and 59-60 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Prentice et al. (US 20100009410, cited on an IDS).
The limitation “for delivery of the system(nucleic acid) of claim 1(56)” does not require the system(nucleic acid) in claim 1 or 56 because the limitation is an intended use of the vector and does not require the instant system or instant nucleic acid. Thus, the broadest reasonable interpretation of the claimed product embraces any vector (viral vector). Paragraph 122 of Prentice discloses viral vectors.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-6, 8-16, 22, 26, 28, 30, 33-34, 41, 42, 56, and 59-60 are rejected under 35 U.S.C. 103 as being unpatentable over Baylor College of Medicine (WO 2017083747) taken with Holly Prentice (US 20100009410), both cited on an IDS.
‘747 discloses a system for modulating gene expression, the system comprises a polynucleotide that comprises in a 5' to 3' direction one or more ligand-binding aptamers comprising at least one polyA cleavage signal therein; and an expressible polynucleotide; the system is exposed to suitable conditions such that when the ligand is not present in the system or its environment, or the ligand does not bind the ligand-binding aptamer, mRNA from the expressible polynucleotide is degraded. In some embodiments, the system is subjected to suitable conditions, such that when the ligand binds the aptamer, mRNA from the expressible polynucleotide is not degraded, and a gene product is expressible from the expressible polynucleotide. For example, see page 3-7, 27-37 and 44-51. ‘747 further discloses a system having the ability to modulate expression of one or more specific genes. The system allows manipulation of expression of the gene(s) by employing a particular ligand that can inhibit the 5' UTR polyA signal-based RNA switch, thereby leading to expression of the gene(s). The system allows tailor-made gene expression using ligands, such as small molecules, to control the expression, including, for example, in a tissue-specific and/or temporal-specific manner. In particular embodiments, the system acts as a biosensor system for using a tailor-made aptamer/expressible polynucleotide combination to provide information about endogenous ligands in a certain environment. The polyA aptamer comprises 2, 3, 4, 5, or more aptamers and are linked along a 5’ to 3’ direction. There may or may not be sequences between the aptamers. The polyA switches comprising SEQ ID NOs: 8, 13, 16, 17, 19, 26, and 28 read instant SEQ ID NO: 4. See page 12 and Figures 11, 19, 21, 24, and 25. The nucleic acid sequence encoding the polypeptide further comprises a 5’ UTR (page 3). Figure 1C and 25 (paragraph 129) disclose a system comprising a GU rich sequence and several MAZ sequences. In cases wherein multiple aptamers are present on a molecule, only one G-rich region is present on the molecule, in specific embodiments, and the G-rich region may be present on the second aptamer (in a 5' to 3' direction) or is present on the 3'-most aptamer of the molecule, in certain cases.
‘747 does not specifically teach inserting the poly A switch into a system comprising a) a 5' splice donor site; b) an engineered intron; c) a first 3’ splice acceptor site; and e) a second 3' splice acceptor site.
However, Prentice teaches a system for modulation of gene expression comprising a 5' splice donor site, an intron, a first 3’ splice acceptor site, a second 3' splice acceptor site, and a nucleic acid sequence encoding an expressible polypeptide. For example, see pages 1-17 and 27. Prentice disclose using a single splice donor to activate alternative splicing from more than one splice acceptor to express multiple polypeptides. Further, teaching expressing the polypeptides at different ratios, or the substitution of different splicing acceptors to control the relative expression of the polypeptides. Prentice also provides a method of regulating polypeptides, the method comprising culturing a cell containing the alternative splicing vector or expression cassette or construct of the present invention, Paragraph 30. FIG. 1 of Prentice shows a schematic of the structural and functional aspects of an alternative splicing vector of the invention which is designed to allow for a single promoter to drive the transcription of a single pre-mRNA which can then be alternatively spliced into two or more transcripts (Paragraph 36). Viral vectors can comprise the system (paragraph 122). FIG. 1 discloses a 5' splice donor site, a first 3' splice acceptor site, a second 3' splice acceptor site, and nucleic acid sequence encoding a polypeptide 3' of the second splice acceptor site.
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify ‘747 with the teaching of Prentice for the purpose of creating a system for modulating gene expression by generating a polyA switch system whose activity can be controlled by flanking said system with splice donor and acceptor sites wherein the switch can be controllably spliced via alternative splicing. See MPEP 2143(I)A and D. The term ‘ligand binding” is an inherent term of any aptamer since an aptamer binds to a target molecule (also known as a ligand). MPEP 2141 II.C. Rationales to support rejections under 35 U.S.C. 103 recites, “Prior art is not limited to the references being applied, but includes the understanding of one of ordinary skill in the art.” In addition, the specification of the instant disclosure does not provide a definition of the term ‘engineered intron’. Paragraph 43 provides an example of the term. The engineered intron could comprise one or more splice sites. The broadest reasonable interpretation of the term embraces any intron that was from an endogenous sequence (e.g. recombinant intron sequence made in a lab or ordered from a company). ‘747 teaches the polyA aptamer comprises 2, 3, 4, 5, or more aptamers in the same orientation or an aptamer can be in the opposite orientation to the other aptamer. Paragraph ‘747 teaches the aptamers in relation one another may have the opposite orientation or same orientation (Fig. 18A and 25). Regarding claim 4, ‘747 discloses wherein the polyA switch comprises a three way junction (3WJ). Paragraph 30; FIG. 8A, A6 comprises a three way junction. Regarding claim 5, ‘747 further discloses wherein the three way junction comprises a junction of a first, a second, and a third double stranded RNA stem. Paragraph 30; FIG. 8A A6 comprises a three way junction comprising three double-stranded RNA stems). ‘747 further discloses wherein the first double stranded RNA stem does not comprise a ligand binding aptamer (FIGS. 8A-8B). See also paragraph 30. FIG. 8A discloses a P1 double-stranded stem without a ligand-binding aptamer. ‘747 further discloses the three way junction comprising at least one single stranded region, each occurring between double stranded stems (paragraph 30, Figure 8A). ‘747 also teaches the three way junction comprising a first, second and third single stranded region, each occurring between the first, second and third double stranded stem (e.g., Figures 8A, 9A, 9B, 9C, 11A). “747 also teaches wherein one or more nucleotides of the polyA cleavage signal are within the three way junction, the third double stranded RNA stem, the third single stranded region, or the first double stranded RNA stem (FIGS. 11A-11B, SEQ ID NO: 8; SEQ ID NO: 9, paragraph 33). A nucleic acid sequence encoding a polypeptide can comprise a 5’ UTR to regulate translation, mRNA stability and contain binding sites for proteins that modulate gene expression. ‘747 teaches that the polyA switches can comprise SEQ ID NOs: 8, 13, 16, 17, 19, 26, and 28 and these sequences comprise a sequence that is 100% identical to instant SEQ ID NO: 4. The 5’ UTR can have one or more 3’ splice acceptor sites to allow splicing of exons into different functional proteins. Paragraph 49 of the as-filed specification discloses that an engineered intron is any sequence. Thus, any intron (CMV) intron taught by Prentice can read on this limitation. ‘747 teaches a construct comprising a G rich region 5’ having MAZ sequences of the nucleic acid encoding the polypeptide and 3’ G-U rich region (paragraph 129 and Figs. 1, 5 and 6 of ‘747). It would have been obvious to try one or more (including four) MAZ sequences to determine the optimal induction of gene expression (see paragraph 14 on page 4 of ‘747). See MPEP 2143(I)E.
To expedite prosecution of the claimed invention considering a possible amendment to claims 41 and 59 to require the system in the vector, the Office will also provide a 103 rejection for a potential amendment considering the potential claims directed to a vector comprising the system. If that amendment to claims 41 and 59 was filed, then a person of ordinary skill in the art would have been obvious to place the system into a viral vector to assist in delivery of the system to a cell (paragraphs 22 and 67 of ‘747).
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claims 7 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over ‘747 and Prentice as applied to claims 1-6, 8-16, 22, 26, 28, 30, 33-34, 41, 42, 56, and 59-60 above, and further in view of Shi (US 20050282190).
‘747 teaches the poly A switch comprising three-ligand binding aptamers.
‘747 and Prentice do not specifically teach the poly A switches comprising a three way junction (3WJ), wherein each double stem region has an aptamer.
However, Shi teaches a 3WJ having three aptamers, wherein each double stem region comprises an aptamer (e.g., pages 3-9, 18-35 and 46-47 and Figures 2 and 3C). Shi teaches, “For the purpose of studying and controlling cellular regulatory networks, it is desirable to have the capability of bridging any pair or bringing together more than two molecules or supra-molecular assemblies, especially proteins.” “A general approach to develop such bridging constructs is to develop two simultaneously available capabilities: the capability of generating ligands to the target proteins or non-proteins at will, and the capability of connecting and recombining these single-site ligands in a single molecular entity at will (paragraph 4).”
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of ‘747 and Prentice taken with Shi to use a 3WJ to connect the three aptamers, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to have the aptamers interact with the same or different target molecules to optimally control inducing nucleic acid sequence expression (pages 6-7 of Shi). ‘747 (Figure 8, 9, 11, 13, 15, and 19) and Shi (Figures 3, 4, 5, 7, 9 and 13-14) teaches double stranded RNA stem between the binding pockets of an aptamer and the general lengths were known to one of ordinary skill in the art. The double stranded RNA stem between the binding pocket of the third aptamer and the three way junction is between 10 and 15 base pairs in length would have been obvious length to optimize the modulation of gene expression. It would have been obvious to one of ordinary skill in the art to include a double-stranded RNA stem of 10-15 base pairs in length between the ligand binding pocket of an aptamer and a three-way junction, since the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. Furthermore, the motivation for doing so would be to optimize distance from a ligand-binding aptamer to the 3-way junction to ensure adequate ligand binding and cleavage at the polyA signal for modulation of expression. Thus, it would have been a simple substitution to make the length between 10 and 15 base pairs in length between the binding pocket of the third aptamer and the three way junction.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claims 27 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over ‘747 and Prentice as applied to claims 1-3, 13, 14, 26, 28, 30, 33-34, 41, 42, 56, and 59-60 above, and further in view of Verhaert et al. (US 20130239236, ‘236).
‘747 and Prentice do not specifically teach the 5’ UTR further comprises a CAA repeat.
However, ‘236 teaches that CAA repeat is an enhancing element (pages 11-12, 22 and 48). ‘236 also teaches an intron comprising a sequence having a sequence of 100 and 200 bases in length (e.g., paragraph 85).
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of ‘747 and Prentice taken with ‘236 to use a CAA repeat in the 5’ UTR, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to enhance expression of the polypeptide. The limitation in instant claim 35 reads on an intron comprising a sequence having 100 and 200 bases in length and is made obvious by ‘236 (paragraph 85). One of ordinary skill in the art could make the system have an intron with at least 100 bases in length taught by ‘326 in the system with a reasonable expectation of success.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claim 37 is rejected under 35 U.S.C. 103 as being unpatentable over ‘747 and Prentice as applied to claims 1-3, 13, 14, 26, 28, 30, 33-35, 41, 42, 56, and 59-60 above, and further in view of Kay et al. (US 20130210897, cited on an IDS).
‘747 and Prentice do not specifically teach the engineered intron is followed by a nucleic acid triplet sequence that modulates the strength of the intron splicing.
However, Kay teaches that an intron can be an intronic cassette comprising an intron and one or more sequences including splice donor sequence, splice acceptor sequence, G triplet sequence, pyrimidine rich tract, consensus point sequence that promote out-splicing of the intron (paragraph 35).
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of ‘747 and Prentice taken with Kay to add a nucleic acid triplet sequence after the intron, namely to arrive at the claimed invention. One of ordinary skill in the art would have been motivated to combine the teaching to use the G triplet sequence to promote the out-splicing of the intron.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Allowable Subject Matter
Claim 39 is objected to as being dependent upon 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. The prior art does not teach or suggest making the construct comprising SEQ ID NOs: 2; 3; or 5 in claim 22 or SEQ ID NOs: 6-56.
There appear to be no prior art references that teach or suggest any sequence with at least any high % identity to SEQ ID NO: 6-65.
The closest prior art for SEQ ID NOs: 2, 3, or 5 are references each disclosing one of the sequences, but they are directed to different publications each containing thousands of sequences. SEQ ID NO: 2 is taught in U.S. Patent No. 7825229, SEQ ID NO: 8376. SEQ ID NO: 3 is taught in U.S. Patent No. 8178503, SEQ ID NO: 138737. SEQ ID NO: 5 is taught in US Patent No. 8090542, SEQ ID NO: 715771. There is nothing in these references or in the prior art teaching or suggesting a skilled artisan to pick these sequence from the thousands of sequences in different publications and using any of these sequences in the system in claim 22.
Conclusion
See attached PTO-326 for disposition of claims.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636