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 on June 07, 2023. Claims 1-39 are currently pending and examined herein.
Priority
The instant application claims priority based on a US Provisional Application No. 63/365,965 filed on June 07, 2022. The provisional application describes the instant SEQ ID NOs: 3 and 4 (Subsection 5.2. Sequences), and reduction to practice of this sequence pair (Figure 3). However, support for the recitation of “a methos of preventing, treating or delaying progression of cancer” and “SEQ ID NOs: 1, 2, 5, and 6” could not be found in this US Provisional Application. Further, it is stated in the instant Provisional Application “we are currently evaluating whether treatment with the S2E3Acc and S2E3Don vivo-morpholinos…to this end, we will initially use the A549 cell model…and subsequently we will use A549-derived tumors in nude mice…" (section "Future developments") which suggests that applicant do NOT have possession of a method of treating cancer because such experimentations have NOT been completed. Accordingly, the effective filling date of instant claims 1-39 is June 07, 2023.
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 deficiency - The incorporation by reference paragraph required by 37 CFR 1.834(c)(1), 1.835(a)(2), or 1.835(b)(2) is missing, defective or incomplete. The Sequence Listing, in ASCII text file is designated UTEP2022-014_SequenceListingXML_2026-01-27.xml and is 6408 B, while the Sequence Listing disclosed in the specification’s incorporation by reference statement is Sequences related to patent application -_SUMO Targeting Morpholines.xml and is 6408 B (pg.1). The names of the ASCII text file do not match.
Required response - Applicant must:
• Provide a substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3), and 1.125 inserting the required incorporation by reference paragraph, 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 Objections
Claims 1, 4-8, 10, 13-17, 19, 22-26, 28, 31, 32, 35, 36, and 39 are objected to because of the following informalities:
Claims 1, 7, 28, and 31 recite “S1E2Acc” and “S1E2Don”, which are acronyms not defined in the instant claims.
Claims 10, 16, 32, and 35 recite “S2E3Acc” and “S2E3Don”, which are acronyms not defined in the instant claims.
Claims 19, 25, 36, and 39 recite “S3E3 Acc” and S3E3Don”, which are acronyms not defined in the instant claims.
Claims 4-6, 8, 13-15, 17, 22-24, and 26 recite “S2V1” and “S2V2”, which are acronyms not defined in the instant claims.
Considering that specific SEQ ID NOs are recited in the claims, it is recommended that Applicant remove these acronyms from the recited claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-27, and 31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1, 10, and 19 recites the limitation "vivo-morpholinos", which renders the claim indefinite due lack of clarity. The instant claims refer to “vivo-morpholinos”, but only recites “morpholinos” earlier in the claims. It is unclear if this recitation is further limiting “morpholinos” (e.g., administering at least 2 morpholinos, wherein the morpholinos are vivo-morpholinos comprising of SEQ ID NOs: 1 or 2) or further limiting “vivo-morpholinos” that are part of the “at least 2 morpholinos” (e.g., administering at least 2 morpholinos, one of them being at vivo-morpholino comprising of SEQ ID NOs: 1 or 2). Although the recitation of “wherein administering at least 2 vivo-morpholinos” is a clear attempt to further limit “vivo-morpholinos”, this term lacks antecedent basis in the instant claims.
Claims 4-6, 8, 13-15, 17, 22-24, and 26 recite the limitation “S2V1” and “S2V2”, which renders the claim indefinite. The specification discloses "performing qRT-PCR…a set of specific primers for transcript-specific amplification is required from the group consisting of S2V1 and/or S2V2" (pg. 4) and "the SUMO2 gene produces two main mature mRNAs: i) SUMO2 variant 1 (S2V1)…and ii) SUMO2 variant 2 (S2V2)" (pg. 7). It is unclear whether the claims are referring to the set of specific primers or SUMO2 variants. It is not clear whether the claims are referring to transcription levels of nucleic acids detected by the specific primers or mRNA quantity of specific SUMO2 variants. It is not clear if the claims are referring to translation levels of SUMO2 variants because they are mature mRNAs. Further, the recited terms are not known in the art to define the scope of the claims.
Those claims included in the statement of rejection but not otherwise discussed are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 2 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 2 recites “comprises administering at least 2-vivo morpholinos” which limitation is already recited in claim 1. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112 – Written Description
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 1-39 are 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.
MPEP 2163.II.A.3.(a).i) states, “Whether the specification shows that applicant was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention”.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. Claims 1, 10, and 19 are drawn to a method of preventing, treating, or delaying progression of cancer, comprising administering a therapeutically effective amount of at least 2 morpholinos. The claims further recite comprising SEQ ID NO: 1, 3, 5, or 2, 4, 6, respectively. Claims 28, 32, and 36 are drawn to compositions comprising said morpholinos. The breadth of the claims is drawn to possession of at least 2 morpholinos with claimed function of therapeutically effective, wherein one of the morpholino is one of the listed sequences, and the remaining one or more could be any sequence targeting any transcript. Thus, the claims encompass a genus of morpholinos that (1) is therapeutically effective and (2) complementary to any transcript.
The specification disclosed the structures of morpholinos and vivo-morpholinos (FIG. 4) and a total of 6 sequences, SEQ ID NOs: 1-6 (pg. 10), each pair targeting one SUMO gene, which are complete structures of only one species of the claimed genus of morpholinos. The specification also disclosed actual reduction to practice of only one pair SEQ ID NOs: 3 and 4 for the instant claim 10 (FIG. 5, pg. 13). The specification fails to disclose any structure of additional species, to what sequences are the morpholinos complementary to as at least 2 morpholinos are required in the instant claims. Without a recognized correlation between structure and function, one of ordinary skill in the art would not be able to identify without further testing which morpholinos complementary to undisclosed transcripts would also be therapeutic effective.
Moulton (Guide for Morpholino Users: Toward Therapeutics. J Drug Discov Develop and Deliv. 2016, 3(2): id1023) teaches the full potential of morpholinos “remain to be developed because there is no available system for systemic delivery that is both non-toxic and highly efficacious” (pg. 11, left-column, third paragraph). Further, considering the mechanism of action of morpholinos serving as translation-blocking agents, “morpholino itself does not cleave the mRNA, this range of possible effects on RNA stability means that the lifetime and concentration of mRNA can be increased, decreased, or unaffected by translation-blocking morpholino treatment” (pg. 6, right-column, third paragraph). Accordingly, morpholinos require empirical testing to determine whether a particular sequence is active and to establish an effective and non-toxic dosage for treatment of a disease, which indicates unpredictability in administering morpholinos as treatment.
Further, dependent claims of claims 1, 10, 19, 28, 32, and 36 are also rejected for depending from a rejected claim and failing to remedy the lack of written description therein.
Based on the preponderance of the evidence, including the relevant teachings of the specification, the absence of working examples, and the state of prior art including the knowledge of morpholinos, one skilled in the art would conclude that Applicant was not in possession of the claimed genus of therapeutically effective morpholinos based on disclosure of SEQ ID NOs: 1-6. Further, Applicant was not in possession of compositions comprising the claimed genus of morpholinos.
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 1-3, 7, 9, and 28-31 are rejected under 35 U.S.C. 103 as being unpatentable over Paschen et al (US 9169519 B2; Published Date: Oct 27, 2015) in view of Moulton (Guide for Morpholino Users: Toward Therapeutics. J Drug Discov Develop and Deliv. 2016, 3(2): id1023), Li et al (Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo; Bioconjugate Chem; 2008, 19:1464–1470), and NC_0000002.12 (Homo sapiens chromosome 2, GRCh38.p14 Primary Assembly, SUMO1 gene from base 202206171 to 202238597, NCBI reference sequence, constructed Apr 06, 2022, 15 pages).
Regarding claims 1-3, Paschen teaches a method for treating cancer in a subject comprising an effective amount of an agent that decreases the levels of SUMO conjugated proteins (Col. 1, lines 54-57; Col. 4, line 40). Paschen further teaches the agent comprises inhibitory RNA complementary to a sequence encoding members of the SUMO conjugation pathway, including SUMO1, SUMO2, or SUMO3, or any combinations thereof , “selected from any of GenBank Accession Nos. NM_001005781.1, NM 001005782.1, NM_03352.4 (SUMO1); NM 001005849.1, NM_006937.3 (SUM02); NM_006936.2 (SUM03)…” (Col. 5, lines 10-43), which are known transcripts of SUMO gene splice variants. Paschen further teaches exemplary miRNA inhibitors targeting SUMO1, SUMO2, and SUMO3 genes (Col. 8, lines 1-6). Thus, Paschen teaches administering at least two inhibitors to decrease levels of SUMO conjugated proteins, and established that the SUMO genes, including their transcript structure, are known targets for RNA interference.
However, Paschen does not teach wherein the inhibitory RNA are morpholinos.
Moulton teaches “morpholinos can be designed to alter splicing of pre-mRNA…targeting either the upstream (5’) end of an intron (the splice donor site) or the downstream (3’) end of an intro (the splice acceptor site)…typically at least 15 bases of intronic sequences are targeted, with the oligo target either abutting or overlapping the exonic sequence…targeting the internal splice sites is most likely to result in splicing out the exon abutting the splice junction, thus excluding that exon from the mature mRNA…for example…exon 2 is directly ligated to exon 4, with exon 3 missing. This exclusion of an exon from a mature mRNA is sometimes called “exon skipping” (pg. 4, left-column). Further, Moulton teaches morpholinos offer several advantages over other antisense oligos which include not requiring catalytic systems (e.g., RICS, RNAse-H) for their activity, having far less off-target interactions, are water-soluble and stable long-term (pg. 11, section “Therapeutic potential”).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Paschen’s inhibitory RNAs to morpholinos as taught by Moulton because it would have merely amounted to a simple substitution of one known element for another to obtain predictable results, as both inhibitory RNAs and morpholinos are both gene-silencing strategies that operate via sequence complementarity. It would have also been obvious because it would have merely amounted to using a known technique (morpholinos targeting splice junctions) to improve similar device (identified SUMO splice variants) in the same way. One would have been motivated to have done so for the advantages and mechanism of action of morpholinos taught by Moulton. One would have had a reasonable expectation of success in doing so because Paschen already teaches a method of targeting SUMO genes and splice variants using inhibitory RNAs, and designing morpholinos complementary to known splice junctions would have been a routine and predictable design.
Further, Moulton teaches “vivo-morpholinos are widely-used and commercially available delivery moiety consisting of an eight-branched dendrimer carrying a guanidinium moiety at each brand tip” (pg. 9, third paragraph). Li also teaches a method of synthesizing vivo-morpholinos by conjugating a morpholino with “a transporter containing a triazine” and successfully delivering vivo-morpholinos that inhibited translation in tissues (pg. 1465, left-column, second paragraph; Fig. 1)
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Paschen’s inhibitory RNAs to vivo-morpholinos as taught by Moulton and Li because it would have merely amounted to applying a known technique to a known device (method or product) ready for improvement to yield predictable results. One would have been motivated to have done so for the advantage of improving morpholinos in vivo delivery into cells and subjects. One would have had a reasonable expectation of success in doing so because Li teaches a method of synthesizing vivo-morpholinos and their delivery in vivo.
As discussed above, Paschen teaches known transcripts of SUMO gene splice variants (Col. 5, lines 10-43) and Moulton teaches the design of morpholinos targeting splice isoforms. However, neither Paschen or Moulton teach SEQ ID NOs: 1 or 2.
SEQ ID NOs: 1 and 2 aligns with the publicly available SUMO1 gene in human chromosome 2 (NCBI Accession Number: NC_0000002.12), specifically at the internal splice site overlapping the exon 2 sequence of transcript NM 001005782.2, a newer version of NM 001005782.1, one of SUMO1 gene splice variants taught by Paschen.
PNG
media_image1.png
430
1783
media_image1.png
Greyscale
PNG
media_image2.png
427
1792
media_image2.png
Greyscale
The obviousness to modify Paschen’s inhibitory RNAs to morpholinos applied above equally applies here. Further, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have further modified Paschen’s inhibitory oligos to the instantly recited sequences because it would have merely amounted to choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success (“obvious to try”). One would have been motivated to have done so because the target gene sequence (SUMO1) and its exon-intron structure were known, and designing morpholinos complementary to those splice junctions would have been routine and predictable design. For instance, SUMO1 splice variant of transcript NM_001005781.1 taught by Paschen is absent of exon 2, and designing morpholinos targeting exon 2 splice sites would arrive at the instantly recited SEQ ID NOs: 1 and 2. One would have had a reasonable expectation of success in doing so because morpholino design is constrained to a finite number of predictable target regions within a known transcript given that morpholino design is not open-ended due to these considerations: at least 15 bases of intronic sequences and the other end of the oligo complementary to either abutting or overlapping the exon sequence, GC content constraints, avoidance of secondary structure, and uniqueness within transcriptome. Therefore, only a finite number of morpholinos can be designed, and the instantly recited sequences represent one of a limited number of predictable morpholino candidates that would have been obtained through routine optimization.
Regarding claims 7, the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 1 or 2 are discussed above as applied to claim 1. Paschen provides one exemplary sequence targeting each SUMO1, SUMO2, and SUMO3 gene (Col. 8, lines 1-6).
Paschen does not teach administering at least two morpholinos targeting the same gene.
Moulton teaches “when two translation-blocking morpholinos target the same mRNA, their combination has greater-than-additive efficacy” (pg. 8, left column, fourth paragraph).
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Paschen’s method to further comprise additional morpholinos targeting the same gene because it would have merely amounted to combining prior art elements according to known methods to yield predictable results. One would have been motivated to have done so for the advantage of maximizing translation-blocking efficiency. One would have had a reasonable expectation of success in doing so because Paschen already teaches a method comprising an inhibitory RNA targeting the same gene.
Regarding claims 9, the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 1 or 2 are discussed above as applied to claim 1. Paschen further teaches “a method of sensitizing a cancer cell to a therapeutic regimen” comprising administering inhibitory RNAs in an amount effective to decrease the levels of SUMO conjugated proteins in the cancer cell (Col. 11, lines 55-58). Sensitizing cancer cells to therapy would have been reasonably understood to prevent or delay the development of resistance to chemotherapy. Accordingly, Paschen’s teachings render obvious the limitation of “inhibiting establishment of chemo resistance”.
Regarding claims 28-31, the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 1 or 2 are discussed above as applied to claim 1. The obviousness to modify Paschen’s method to include additional morpholinos are discussed above as applied to claims 7. Further, Paschen teaches the inhibitory RNAs are “administered in a pharmaceutically acceptable composition” (Col. 12, lines 18-20), which positively meets the claim limitations recited in the instant claims.
Claims 4-6, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Paschen et al (US 9169519 B2; Published Date: Oct 27, 2015) in view of Moulton et al (Using Morpholinos to Control Gene Expression; Current Protocols in Molecular Biology, 2008, unit 26.8:26.8.1-26.8.29), Li et al (Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo; Bioconjugate Chem; 2008, 19:1464–1470), and NC_0000002.12 (Homo sapiens chromosome 2, GRCh38.p14 Primary Assembly, SUMO1 gene from base 202206171 to 202238597, NCBI reference sequence, constructed Apr 06, 2022, 15 pages) as applied to claims 1 above, and further in view of NC_000017.11 (Homo sapiens chromosome 17, GRCh38.p14 Primary Assembly, SUMO2 gene from base 75165586 to 75182959, NCBI reference sequence, constructed Apr 06, 2022, 7 pages).
Regarding claims 4-6, the obviousness to modify Paschen’s inhibitory oligos to morpholinos are discussed above as applied to claim 1. Regarding “S2V1” and “S2V2”. the specification teaches S2V1 is SUMO2 gene splice variant 1, transcript NM_006937.4, and S2V2 is SUMO2 gene splice variant 2, transcript NM_001005849.2 (FIG. 2).
Paschen does not explicitly teach reducing SUMO2 gene splice variant 1 or increasing SUMO2 gene splice variant 2.
The instantly recited SEQ ID NOs: 3 and 4 aligns with the publicly available SUMO2 gene in human chromosome 17 (NCBI Accession Number: NC_000017.11), specifically at the internal splice site overlapping the exon 3 sequence of transcript NM_006937.4, a newer version of NM_006937.3, one of SUMO2 gene splice variants taught by Paschen.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filling date of the invention to have modified Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NO: 3 or 4 because it would have merely amounted to choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success (“obvious to try”) as morpholino design is constrained to a finite number of predictable target regions within a known transcript as discussed above and applied to claim 1 for SEQ ID NOs: 1 and 2. Following this modification, Paschen’s method targeting splice junction at exon 3 of SUMO2 gene, in addition to targeting SUMO1 gene, would have resulted in increased translation of SUMO2 gene splice variant 2 lacking exon 3, and reduced translation of SUMO2 gene splice variant 1 containing exon 3.
PNG
media_image3.png
483
1714
media_image3.png
Greyscale
PNG
media_image4.png
471
1597
media_image4.png
Greyscale
Regarding claims 8, the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 1 and 2 discussed above as applied to claim 7 combined with the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 3 or 4 discussed above as applied to claim 4, the instant claim limitations are met.
Claims 10-18, and 32-35 are rejected under 35 U.S.C. 103 as being unpatentable over Paschen et al (US 9169519 B2; Published Date: Oct 27, 2015) in view of Moulton (Guide for Morpholino Users: Toward Therapeutics. J Drug Discov Develop and Deliv. 2016, 3(2): id1023), Li et al (Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo; Bioconjugate Chem; 2008, 19:1464–1470), as applied to claims 1-3 above, and further in view of NC_000017.11 (Homo sapiens chromosome 17, GRCh38.p14 Primary Assembly, SUMO2 gene from base 75165586 to 75182959, NCBI reference sequence, constructed Apr 06, 2022, 7 pages).
Regarding claims 10-15, the obviousness to modify Paschen’s inhibitory oligos to vivo-morpholinos, particularly comprising SEQ ID NOs: 3 or 4 are discussed above as applied to claims 1-3, and 4-6, respectively.
Regarding claims 16-17, the obviousness to modify Paschen’s inhibitory oligos to morpholinos comprising SEQ ID NOs: 3 or 4 equally applies here as to claims 4-6. The obviousness to further modify Paschen’s method to target SUMO genes using additional morpholinos, SEQ ID NOs: 3 and 4 is discussed above as applied to claims 7 and 8.
Regarding claim 18, the teachings of Paschen on inhibiting establishment of chemo resistance is discussed above as applied to claim 9.
Regarding claims 32-35, the obviousness discussed above as applied to claims 10-17 equally applies here. Paschen further teaches the inhibitory RNAs are “administered in a pharmaceutically acceptable composition” (Col. 12, lines 18-20), which meets the instantly recited claim limitations.
Claims 19-21, 25, 27, 36-39 are rejected under 35 U.S.C. 103 as being unpatentable over Paschen et al (US 9169519 B2; Published Date: Oct 27, 2015) in view of Moulton (Guide for Morpholino Users: Toward Therapeutics. J Drug Discov Develop and Deliv. 2016, 3(2): id1023), Li et al (Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo; Bioconjugate Chem; 2008, 19:1464–1470), as applied to claims 1-3 above, and further in view of NC_000021.9 (Homo sapiens chromosome 21, GRCh38.p14 Primary Assembly, SUMO3 gene from base 44805617 to 44818062, NCBI reference sequence, constructed Apr 06, 2022, 6 pages) and NM_001286416.2 (Homo sapiens small ubiquitin like modifier 3 (SUMO3), transcript variant 2, mRNA, NCBI reference sequence, priority to Apr 21, 2022).
Regarding claims 19-21, the obviousness to modify Paschen’s inhibitory oligos to vivo-morpholinos are discussed above as applied to claims 1-3.
However, Paschen does not teach the instantly recited SEQ ID NOs: 5 or 6.
SEQ ID NOs: 5 and 6 aligns with SUMO3 gene in human chromosome 21 (NCBI Accession Number: NC_000021.9), specifically at the internal splice site overlapping the exon 3 sequence of transcript NM_006936.3, a newer version of NM_006936.2 recited by Paschen. Another SUMO3 gene transcript NM_001286416.2 also demonstrates an additional SUMO3 gene splice variant, lacking exon 3, was known in the art. Accordingly, designing morpholinos to skip exon 3 of SUMO3 gene would arrive to the instantly recited SEQ ID NOs: 5 and 6, which therefore represents predictable antisense candidates derived from a known transcript sequence, and its selection would have been the result of routine morpholino design and optimization. Thus, the obviousness rationale and reasonable expectation of success discussed above in claim 1 apply equally to claims 19-21.
PNG
media_image5.png
484
1784
media_image5.png
Greyscale
PNG
media_image6.png
487
1788
media_image6.png
Greyscale
Regarding claim 25, the obviousness to further modify Paschen’s method to target SUMO genes using additional morpholinos, SEQ ID NOs: 5 and 6 is discussed above as applied to claim 7.
Regarding claim 27, the teachings of Paschen on inhibiting establishment of chemo resistance is discussed above as applied to claim 9.
Regarding claims 36-39, the obviousness discussed above as applied to claims 19-21 and 25 equally applies here. Paschen further teaches the inhibitory RNAs are “administered in a pharmaceutically acceptable composition” (Col. 12, lines 18-20), which meets the instantly recited claim limitations.
Claims 22-24, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Paschen et al (US 9169519 B2; Published Date: Oct 27, 2015) in view of Moulton (Guide for Morpholino Users: Toward Therapeutics. J Drug Discov Develop and Deliv. 2016, 3(2): id1023), Li et al (Design and Synthesis of Dendritic Molecular Transporter that Achieves Efficient in Vivo Delivery of Morpholino Antisense Oligo; Bioconjugate Chem; 2008, 19:1464–1470), NC_000021.9 (Homo sapiens chromosome 21, GRCh38.p14 Primary Assembly, SUMO3 gene from base 44805617 to 44818062, NCBI reference sequence, constructed Apr 06, 2022, 6 pages) and NM_001286416.2 (Homo sapiens small ubiquitin like modifier 3 (SUMO3), transcript variant 2, mRNA, NCBI reference sequence, priority to Apr 21, 2022) as applied to claims 19-21, and 25 above, and further in view of NC_000017.11 (Homo sapiens chromosome 17, GRCh38.p14 Primary Assembly, SUMO2 gene from base 75165586 to 75182959, NCBI reference sequence, constructed Apr 06, 2022, 7 pages).
Regarding claims 22-24, and 26, the obviousness to modify Paschen’s inhibitory to morpholinos, particularly SEQ ID NOs: 5 and 6 is discussed above as applied to claims 19-21 and 25. The obviousness to modify Paschen’s method to target SUMO genes with additional morpholinos, particularly SEQ ID NOs: 3 and 4 is discussed above as applied to claims 4-6. Further, following this modification, Paschen’s method targeting splice junction at exon 3 of SUMO2 gene, in addition to targeting SUMO3 gene, would have resulted in increased translation of SUMO2 gene splice variant 2 lacking exon 3, and reduced translation of SUMO2 gene splice variant 1 containing exon 3.
Conclusion
No claims are allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to QIWEN SU-TOBON whose telephone number is (571)272-0331. The examiner can normally be reached Monday - Friday, 9:30am-5:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammel can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
QIWEN SU-TOBON
Examiner
Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636