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 .
Claims 1-17 and 19 are pending as amended 10/25/23, and are considered herein.
Formalities:
The drawings of 10/25/23 are accepted.
The specification of 5/14/24 is accepted.
The IDS filings of 12/4/23; 7/19/24; 12/19/24; and 1/12/26 have been considered and are signed-off upon, herewith.
Claim Objections
Applicant is advised that should claim 6 be found allowable, claim 12 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 6 requires the nucleic acid of Claim 1 to be integrated into a viral vector, while Claim 12 recites an expression comprising the nucleic acid of Claim 1. In both instances the nucleic acid is integrated into the same nucleic acid as the viral vector. Thus, despite a slight difference in wording, these claims have substantially the same scope.
Applicant is advised that should claim 7 be found allowable, claim 15 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). Claim 7 requires the nucleic acid of Claim 1 to integrated into a viral vector. Claim 12 recites the viral vector comprising the nucleic acid of Claim 1. In both instances, the viral vector comprises the nucleic acid of claim 1. Thus, despite a slight difference in wording, these claims have substantially the same scope.
Claim Rejections - 35 USC § 112
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 14 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 14 depends from Claim 13, which is a cell comprising an expression vector comprising the nucleic acid of Claim 1, but is drawn to the protein produced from the cell. The protein is neither the cell, the vector, or the nucleic acid, and thus is outside the scope of Claim 13. 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 17 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 17 depends from Claim 16, which is to the viral vector made from the cell comprising the viral vector of Claim 16, the viral vector comprising the nucleic acid of Claim 1. However, Claim 17 is drawn to the viral vector made, and thus, is outside the scope of it’s parent claim. 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 § 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.
Claim(s) 1-6 and 12-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over (i) Nakamori, et al. (2011) “Myotonic Dystrophy: Therapeutic Approaches to RNA Toxicity”, Brain and Nerve, 63(11): 1161-68 (more than a year before earliest filing date) and (ii) U.S. Patent Application Publication No. 2014/0335521 A1, to Nakamura, et al. (Publication more than a year before earliest filing date). As the Nakamori 2011 document in Brain and Nerve is in Japanese, the Examiner is relying on the description in the PCT document, provided in the English translation for PCT/JP2022/019038 in Applicant’s PCT, of record.
In the English translation of the PCT/JP2022/019038, it is stated that Nakamori, pages 1162 through 1165, teach that myotonic dystrophy type 1 (DM1) is due to abnormal RNA having expanded CUG repeats, the expanded CUG repeats assume hairpin structure and form RNA aggregates in the nucleus, and such RNA CUG sequences bind to MBNL1 protein (which typically regulates RNA splicing and has high binding affinity for the CUG sequences), thereby sequestering the MBNL protein and stopping it from acting to guide normal alternative splicing functions, resulting in DM1. Further Nakamori teaches known therapeutic approaches are to target the abnormal polyCUG sequences, through RNAses that break it down, antisense oligonucleotide morpholina (CAG) 25, which targets the expanded CUG, and administration of the same reduces RNA aggregates and frees MBNL1 to act on RNA splicing. Lastly, low-molecular weight compounds that inhibit the polyCUG and MBNL binding have been identified and it inhibits aggregate formations in DM1 model cells.
The Artisan, interested in binding RNA, would be aware of Nakamura. Nakamura teaches the design of RNA binding proteins, using PPR motifs (ABSTRACT; paragraph 16). The protein itself has at least one PPR motif (preferably 2 to 14), each consisting of a polypeptide of 30-38 amino acids, following formula 1 (paragraph 17). Helix A is 12 amino acids long and can form an alpha helix structure, represented by formula 2 (paragraph 18), where A1 to A12 of formula 2 may be an amino acid (paragraph 19), X of formula 1 may be absent or a moiety of 1-9 amino acids long (paragraph 19), helix B of formula 1 is 11-13 amino acids and can form an alpha helix (paragraph 20), L of formula 1 is 2-7 amino acids long, represented by formula 3, and labeling amino acids 1-7 from the C terminal end to the N-terminal side, with Liii-Lvii not being required to be present (paragraphs 21-22), and the combination of A1, A4, and Lii, or the combination of A4 and L2 in each motif may be chosen according to each base, so that each such PPR motif binds to C, U, or G (paragraph 24). Additionally, the protein may be linked to a protein for degradation of the RNA, including, e.g., and RNAse (e.g., paragraph 102).
Returning to Nakamori, the document describes directly breaking down abnormal RNA with CUG repeats using an RNAse, and treating DM1 with compounds that target CUG repeats to inhibit RNA aggregate formation and binding of MBNL1, but does not specify the particular compound of Claim 1, for such binding.
However, target-specific degradation or a known method that can inhibit the binding capability of the target molecule are taught by Nakamura, and it can bind and target the polyCUG, blocking MBNL1 binding, and, in the instance of a linked RNAse, would further degrade the RNA.
Thus, at the time of invention, it would be obvious to make the claimed structure of Claim 1. The Artisan would do so to treat, at the very least, DM1 in cells. The Artisan would expect success, as the elements are utilized for art-recognized purposes.
Claims 2-3: As above, 2-14 PPR motifs are preferable in Nakamura (e.g., paragraph 17).
Claim 4: e.g., paragraph 24 teaches the same embodiments of A1, A4, and Lii.
Claim 5: e.g., paragraph 24 teaches the same embodiments of A4 and Lii.
Claim 6: paragraph 101 of Nakamura teaches making nucleic acids encoding the protein, cloning it, and preparing a transformant that produces the protein, which inherently teaches the expression vector.
Claim 12: paragraph 101 of Nakamura teaches making nucleic acids encoding the protein, cloning it, and preparing a transformant that produces the protein, which inherently teaches the expression vector.
Claim 13: paragraph 101 of Nakamura teaches making nucleic acids encoding the protein, cloning it, and preparing a transformant that produces the protein, which inherently teaches the expression vector in a cell.
Claim 14: paragraph 101 of Nakamura teaches making nucleic acids encoding the protein, cloning it, and preparing a transformant that produces the protein
Claim(s) 1-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nakamori, et al. (2011) “Myotonic Dystrophy: Therapeutic Approaches to RNA Toxicity”, Brain and Nerve, 63(11): 1161-68 (more than a year before earliest filing date) and (ii) U.S. Patent Application Publication No. 2014/0335521 A1, to Nakamura, et al. (Publication more than a year before earliest filing date) as applied to claim1-6 and 12-14, above, and further in view of Zhang, et al. (2014) “Treatment of Type 1 Myotonic Dystrophy by Engineering Site-Specific RNA Endonucleases that Target (cug)n Repeats”, Molecular Therapy, 22(2): 312-20 and Tang, et al. (2010) “AAV-directed muscular dystrophy gene therapy”, Expert Opinion in Biological Therapy, 10(3): 395-408.
As shown above, the base claims (1-6 and 12-14) are obvious over Nakamori and Nakamura, alone. However, the aspects of utilizing a Lentiviral or AAV vectors, and e.g., AAV1, AAV2, AAV6, AAV8, and AAV9, are not taught or obvious over the base art.
On the other hand, Zhang, who the Artisan would be aware of for its teaching of targeting the CUG repeats with nucleases, teaches the transfection of DM1 fibroblasts with MyoD gene, utilizing a lentiviral vector, and differentiation of the same into myoblasts and myocytes, and demonstrating treatment of the same with their RNA endonucleases targeting the CUG repeats (e.g., pp. 314-315). Further, the Artisan, interested in delivering vectors encoding the nuclease would also be aware of Tang for teaching delivery of transgenes to muscle cells via AAV vectors, specifically AAV1, AAV2, AAV6, AAV8 and AAV9, specifically targeting muscle cells (e.g., p. 396, col. 1, penultimate paragraph).
Thus, at the time of invention, it would have been obvious to use lentiviral, AAV1, AAV2, AAV6, AAV8, and AAV9 vectors to encode the protein, and deliver the same to the DM1 fibroblasts, myoblasts and myocytes of Zhang. The Artisan would do so to treat the DM1 in these cells. The Artisan would expect success, as the components are utilized for art-recognized purposes.
Claim(s) 1-17 and 19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nakamori, et al. (2011) “Myotonic Dystrophy: Therapeutic Approaches to RNA Toxicity”, Brain and Nerve, 63(11): 1161-68 (more than a year before earliest filing date) and (ii) U.S. Patent Application Publication No. 2014/0335521 A1, to Nakamura, et al. (Publication more than a year before earliest filing date) as applied to claim1-6 and 12-14, above, and further in view of Zhang, et al. (2014) “Treatment of Type 1 Myotonic Dystrophy by Engineering Site-Specific RNA Endonucleases that Target (cug)n Repeats”, Molecular Therapy, 22(2): 312-20 and Tang, et al. (2010) “AAV-directed muscular dystrophy gene therapy”, Expert Opinion in Biological Therapy, 10(3): 395-408, as applied to claims 1-17 above, and further in view of Jauvin, et al. (2017) “Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice”, Molecular Therapy: Nucleic Acids, 7: 465-74.
As shown above, the base art makes Claim 1-17 obvious, however the aspect of treating a subject, while the object of the work, is not taught or obvious from the Art cited.
On the other hand, the Artisan, interested in treating DM1 with the compounds, would also be aware of Jauvin, for similar targeting of the CUG repeats in DM1 Mice. Jauvin teaches that use of ASOs for targeting the CUG repeats can reverse a subset of mis-spliced RNAs (e.g., p. 465, col. 2, paragraph 3), and their method of treating of the mouse produced sustained phenotypic disease reversal (e.g., DISCUSSION), the method including administration of the ASOs subcutaneously (p. 471).
Thus, at the time of invention, it would have been obvious to make the vectors and deliver them to the cells of the mouse, via the vectors, in order treat the mouse DM1. The Artisan would expect success, as the components are utilized for art recognized purposes and were already known to work, and work through similar methods.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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, Tracy Vivlemore can be reached at 571-272-2914. 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.
ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638