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 .
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 FIGs. 1A-1B, 13A-13E, 14A-14C, 15A-15C, 16A-16C, and 17A-17B 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.
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.
Claim Interpretation
Claim 1 recites "a siRNA that is processed by cellular RNAi machinery to produce one or more siRNAs." This is a product-by-process claim. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by- process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (MPEP 2113(I)).
Claim Rejections - 35 USC § 112
Claim 6-7 and 11 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.
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 6-7 and 11 recites the limitation "the different genes" in line 1 of the claims. There is insufficient antecedent basis for this limitation in the claim. It is unclear if the claims are meant to specifically limit the claims to the presence of multiple genes or if the claims are directed towards the broader embodiment of claims 1 and 4 wherein only a single target is required and the single gene may be selected from those in claims 6-7 and 11. Further, it is unclear if the claimed “different genes” present in claim 11 are meant to be limited to the targets present in claim 4 or if the “different genes” may be any gene because claims 1 and 10 (i.e., the claims from which claim 11 ultimately depends) does not recite any specific genes.
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.
Claim(s) 1-5 and 9-10 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987).
Regarding claim 1, Herrmann is drawn towards a study concerned with the use of a covalently linked siRNA to an aptamer that selectively binds CTLA4, termed “CTLA4apt-siRNA”, and allows for the gene silencing of STAT3 through the processing of the siRNA in exhausted CD8+ T cells (i.e., a construct comprising an aptamer that specifically binds at least one target protein on an immune cell and an siRNA that is processed by cellular machinery to produce one or more siRNAs) (Abstract, pg. 2977-2978; see Fig. 1 and Supplementary Fig. 1).
Regarding claim 2, Herrmann teaches that the cell of the immune system is a T cell (Abstract, pg. 2977-2978; see Fig. 1).
Regarding claims 3 and 9-10, Herrmann teaches that the target protein is CTLA-4 (Abstract, pg. 2977-2978; see Fig. 1).
Regarding claims 4-5, Herrmann teaches that the siRNA targets STAT3 (Abstract, pg. 2977-2978; see Fig. 1).
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.
Claim(s) 6-7 and 11 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10 above, and further in view of Nowyhed ("The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3." Scientific reports 5.1 (2015): 9059).
Regarding claims 6-7 and 11, Herrmann anticipates claims 1-5 and 9-10 as described above. For the purposes of examination, the claims are interpreted as requiring the presence of a single gene selected from the claimed different genes NR4A1 and VHL.
Herrmann does not teach or suggest that the siRNA targets NR4A1 (Claims 6-7 and 11).
Nowyhed is drawn towards a study concerned with how NR4A1 controls T cell development (Abstract). Nowyhed teaches the knockdown of NR4A1 expression in T cells through the use of an siRNA directed against the NR4A1 gene (pg. 4-5; see Figure 3). Nowyhed teaches that loss of NR4A1 expression results in increased Runx3 expression in thymocytes which consequently causes a 2-fold increase in the frequency and total number of intrathymic and peripheral CD8+ T cells (Abstract). Nowyhed teaches that selective manipulation of Nr4a1 expression may serve as a potential strategy to boost CD8 T cell response against infection and during vaccination through its manipulation of Runx3 (pg. 7).
Therefore, 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 siRNA sequence of Herrmann such that it targeted NR4A1 because it would have merely amounted to a simple substitution of one known siRNA sequence for another. Because each of the two siRNA molecules were used in a similar way, namely for the knockdown of a target gene’s expression within a T cell, then it would have been predictable to have used the NR4A1 siRNA sequence within the construct of Herrmann. And because Nowyhed teaches that silencing NR4A1 resulted in an increased presence of peripheral T cells and a beneficial immune response, one would have been motivated to do so.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10 above, and further in view of Prodeus ("Targeting the PD-1/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers." Molecular therapy Nucleic acids 4 (2015)).
Regarding claim 8, Herrmann anticipates claims 1-5 and 9-10 as described above.
Herrmann does not teach or suggest that the target protein comprises PD-1 (Claim 8).
Prodeus is drawn towards a study concerned with targeting PD-1 with DNA aptamers for the treatment of disseminated cancers (Abstract). Prodeus teaches that PD-1 is a protein that is expressed on the surface of activated T cells and can be targeted by anti-PD-1 DNA aptamers (pg. 1-3, see Figure 1). Prodeus teaches that the anti-PD-1 aptamers can be utilized to promote strong antitumor immune responses (pg. 5).
Therefore, 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 aptamer of Herrmann such that it binds to PD-1 because it would have merely amounted to a simple substitution of one known aptamer that can target T cells for another. Because each of the two aptamers were used in a similar way, namely for the targeting of proteins expressed on the surface of T cells, then it would have been predictable to have used the anti-PD-1 aptamer within the construct of Herrmann to silence STAT3 expression in T cells. And because Prodeus teaches that the anti-PD-1 aptamers can be used to promote antitumor immune activity, one would have been motivated to do so.
Claim(s) 12-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10 above, and further in view of Liu (Us Patent No. 10,960,086 B2, published 30 March 2021, filed 28 December 2018).
Regarding claims 12-15, Herrmann anticipates claims 1-5 and 9-10 as described above.
Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claims 12-13), wherein the linker is a poly-adenosine linker (Claims 14-15).
Liu is drawn towards an invention concerned with an aptamer platform capable of silencing one or more genes in vivo (Abstract). Liu teaches the use of an aptamer-siRNA construct comprising two HER2 aptamers flanking an EGFR siRNA, wherein the aptamers and siRNA molecules are linked to one another though the use of adenosine linkers (Col 3, lines 58067; see Fig. 1A). Liu teaches that the linkers may comprise unpaired poly-adenosines present between the siRNA and aptamers (Col. 8, lines 20-25). Liu teaches that the linker helps to warrant the siRNA cleavage with dicer, since dicer is able to measure and cut 21-25 nt RNA duplexes (Col. 8, lines 20-25).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added an unpaired poly-adenosine linker between each siRNA and aptamer because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because each of the two aptamer-siRNA chimeras were used in a similar way, namely for the knockdown of a target gene’s expression within a cell through the use of a chimera comprising an siRNA and aptamers that can be processed by cellular machinery to produce one or more siRNAs, then it would have been predictable to have used the unpaired poly-adenosine linker within the construct of Herrmann and position it between the aptamer and siRNA. And because Liu teaches that the linkers allowed for cleavage of the siRNA by dicer, one would have been motivated to do so.
Regarding claim 16, the applicable teachings of Herrmann are discussed above as applied claims 1-5 and 9-10.
While Herrmann teaches that the first end comprises an aptamer that binds to CTLA-4, Herrmann does not teach or suggest that the second end comprises an aptamer that binds to CTLA-4 (Claim 16). Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claim 16).
The teachings of Liu and the obviousness rationale as applied to the unpaired adenosine linkers are discussed above as applied to claims 12-15. Liu further teaches that the two aptamers flanking the EGFR siRNA may be directed towards the same HER2 protein (Col 3, lines 58067; see Fig. 1A). Liu teaches that using multiple aptamers specific to a cell surface protein increases efficiency of delivering the siRNAs to the targeted cell (Col 3, lines 24-26).
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed second end comprising an aptamer that binds to CTLA4 because it would have merely amounted to a simple combination of prior art elements according to known methods to yield predictable results. Because Liu teaches using a second aptamer present on a second side of an siRNA for a similar purpose as Herrmann, namely the silencing of a target gene in a cell, then one would have had a reasonable le expectation of success in using a second aptamer directed towards CTLA4 on the second end of the construct of Herrmann in order to silence STAT3 expression. And because Liu teaches that the second aptamer allows for better targeting efficiency, then one would have been motivated to do so.
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.
Claim 1-5 and 9-10 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/558,951 (reference application) in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 4 claims a therapeutic composition comprising a ligand that specifically binds at least one target protein and a cytotoxin that is processed by cellular RNAi machinery to produce one or more siRNAs wherein at least one of said siRNAs specifically inhibits the expression of one or more different genes.
Copending claim 4 does not claim that the target protein is on a cell of the immune system (Claim 1). Copending claim 4 does not claim that the cell is a T cell (Claim 2). Copending claim 4 does not claim that the target protein is CTLA-4 (Claims 3 and 9-10). Copending claim 4 does not claim that the siRNA targets STAT3 (Claims 4-5).
The applicable teachings of Herrmann are described above as applied to claims 1-5 and 9-10.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed target protein because it would have merely amounted to a simple substitution of one known aptamer, siRNA sequence, and cell type for another to yield predictable results. Since the copending claims claim the use of an aptamer-siRNA construct for the same purpose as Herrmann, namely the targeting of an siRNA to a target cell of interest, it would have been predictable to have similarly made and used an aptamer that targets a CTLA4 protein on a cell of the immune system to direct an siRNA to silence STAT3 in the immune cell.
Claim 6-7 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/558,951 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Nowyhed ("The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3." Scientific reports 5.1 (2015): 9059).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 6-7 and 11, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 4 in view of Herrmann does not teach or suggest that the siRNA targets NR4A1 (Claims 6-7 and 11).
The applicable teachings of Nowyhed are discussed above as applied to claims 6-7 and 11.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 6-7 and 11 above.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/558,951 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Prodeus ("Targeting the PD-1/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers." Molecular therapy Nucleic acids 4 (2015))
Regarding claim 8, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 4 in view of Herrmann does not teach or suggest that the target protein comprises PD-1 (Claim 8).
The applicable teachings of Prodeus are discussed above as applied to claim 8.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 8 above.
Claims 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/558,951 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Liu (Us Patent No. 10,960,086 B2, published 30 March 2021, filed 28 December 2018).
Regarding claims 12-16, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 4 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claims 12-13), wherein the linker is a poly-adenosine linker (Claims 14-15). Copending claim 4 in view of Herrmann does not teach or suggest that the second end comprises an aptamer that binds to CTLA-4 (Claim 16). Copending claim 4 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claim 16).
The applicable teachings of Liu are discussed above as applied to claim 12-16.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 12-16 above.
Claim 1-5 and 9-10 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 18/289,519 (reference application) in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, copending claim 5 claims an aptamer-siRNA construct comprising:a) a first end and second end comprising an aptamer that specifically binds at least one target protein; and
b) a siRNA construct between the first and second ends, wherein i. the siRNA construct is processed by cellular RNAi machinery to produce one or more siRNAs wherein the siRNA molecule is selected from SEQ ID NO: 1 to SEQ ID NO: 594 from Table 1.
Copending claim 5 does not claim that the target protein is on a cell of the immune system (Claim 1). Copending claim 5 does not claim that the cell is a T cell (Claim 2). Copending claim 5 does not claim that the target protein is CTLA-4 (Claims 3 and 9-10). Copending claim 5 does not claim that the siRNA targets STAT3 (Claims 4-5).
The applicable teachings of Herrmann are discussed above as applied to claim 1-5 and 9-10.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed target protein because it would have merely amounted to a simple substitution of one known aptamer, siRNA sequence, and cell type for another to yield predictable results. Since the copending claims claim the use of an aptamer-siRNA construct for the same purpose as Herrmann, namely the targeting of an siRNA to a target cell of interest, it would have been predictable to have similarly made and used an aptamer that targets a CTLA4 protein on a cell of the immune system to direct an siRNA to silence STAT3 in the immune cell.
Claim 6-7 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 18/289,519 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Nowyhed ("The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3." Scientific reports 5.1 (2015): 9059).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 6-7 and 11, copending claim 5 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 5 in view of Herrmann does not teach or suggest that the siRNA targets NR4A1 (Claims 6-7 and 11).
The applicable teachings of Nowyhed are discussed above as applied to claims 6-7 and 11.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 6-7 and 11 above.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 18/289,519 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Prodeus ("Targeting the PD-1/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers." Molecular therapy Nucleic acids 4 (2015))
Regarding claim 8, copending claim 5 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 5 in view of Herrmann does not teach or suggest that the target protein comprises PD-1 (Claim 8).
The applicable teachings of Prodeus are discussed above as applied to claim 8.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 8 above.
Claims 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of copending Application No. 18/289,519 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Liu (Us Patent No. 10,960,086 B2, published 30 March 2021, filed 28 December 2018).
Regarding claims 12-16, copending claim 5 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 5 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claims 12-13), wherein the linker is a poly-adenosine linker (Claims 14-15). Copending claim 5 in view of Herrmann does not teach or suggest that the second end comprises an aptamer that binds to CTLA-4 (Claim 16). Copending claim 5 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claim 16).
The applicable teachings of Liu are discussed above as applied to claim 12-16.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 12-16 above.
Claims 1-5 and 9-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/289,514 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987).
This is a provisional nonstatutory double patenting rejection.
Regarding claim 1, copending claim 4 recites “an aptamer-siRNA chimera comprising an aptamer that specifically binds at least one target protein and an siRNA construct that is processed by cellular RNAi machinery to produce one or more siRNAs wherein at least one siRNA specifically inhibits expression of two or more different genes” (see copending claim 4).
Copending claim 4 does not claim that the target protein is on a cell of the immune system (Claim 1). Copending claim 4 does not claim that the cell is a T cell (Claim 2). Copending claim 4 does not claim that the target protein is CTLA-4 (Claims 3 and 9-10). Copending claim 4 does not claim that the siRNA targets STAT3 (Claims 4-5).
The applicable teachings of Herrmann are described above as applied to claims 1-5 and 9-10.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have arrived at the requirements of the claimed target protein because it would have merely amounted to a simple substitution of one known aptamer, siRNA sequence, and cell type for another to yield predictable results. Since the copending claims claim the use of an aptamer-siRNA construct for the same purpose as Herrmann, namely the targeting of an siRNA to a target cell of interest, it would have been predictable to have similarly made and used an aptamer that targets a CTLA4 protein on a cell of the immune system to direct an siRNA to silence STAT3 in the immune cell.
Claim 6-7 and 11 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/289,514 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10 above, further in view of Nowyhed ("The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3." Scientific reports 5.1 (2015): 9059).
This is a provisional nonstatutory double patenting rejection.
Regarding claims 6-7 and 11, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 4 in view of Herrmann does not teach or suggest that the siRNA targets NR4A1 (Claims 6-7 and 11).
The applicable teachings of Nowyhed are discussed above as applied to claims 6-7 and 11.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 6-7 and 11 above.
Claim 8 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/289,514 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Prodeus ("Targeting the PD-1/PD-L1 immune evasion axis with DNA aptamers as a novel therapeutic strategy for the treatment of disseminated cancers." Molecular therapy Nucleic acids 4 (2015))
Regarding claim 8, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 4 in view of Herrmann does not teach or suggest that the target protein comprises PD-1 (Claim 8).
The applicable teachings of Prodeus are discussed above as applied to claim 8.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 8 above.
Claims 12-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of copending Application No. 18/289,514 in view of Herrmann ("CTLA4 aptamer delivers STAT3 siRNA to tumor-associated and malignant T cells." The Journal of clinical investigation 124.7 (2014): 2977-2987) as applied to claims 1-5 and 9-10, further in view of Liu (Us Patent No. 10,960,086 B2, published 30 March 2021, filed 28 December 2018).
Regarding claims 12-16, copending claim 4 in view of Herrmann renders obvious claims 1-5 and 9-10 as described above.
Copending claim 5 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claims 12-13), wherein the linker is a poly-adenosine linker (Claims 14-15). Copending claim 5 in view of Herrmann does not teach or suggest that the second end comprises an aptamer that binds to CTLA-4 (Claim 16). Copending claim 5 in view of Herrmann does not teach or suggest that the construct further comprises unpaired linker comprising 2-6 adenines between each siRNA and each aptamer (Claim 16).
The applicable teachings of Liu are discussed above as applied to claim 12-16.
Therefore, it would have been obvious to have modified the copending application for the same reasons discussed above in the obviousness rationale utilized in the 35 USC 103 rejection of claims 12-16 above.
Conclusion
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/KYLE T REGA/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
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