DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restriction
Applicant’s election without traverse of Group I (claims 1, 2, 19, 23, 62, 69, 76, 78, 86, 88, 89, 91 and 92) in the reply filed on 02/26/2026 is acknowledged.
Applicant’s statement that Claims 1, 2, 19, 23, 62, 69, 76, 78, 86, 88, 89, 91, 92 and 124- 130 encompass the elected invention is acknowledged.
Applicant filed an amended claim set with new claims 124-130 and cancelled Claims 44, 45, 95, 96, 104, 107, 110, and 118 as being drawn to non-elected inventions.
Therefore, claims 1-2, 19, 23, 62, 69, 76, 78, 86, 88-89, 91-92, and 124-130 are pending and are under examination in this office action.
Priority
This application is claiming the benefit of provisional applications Nos. 63/328,241 filed on 04/06/2022 and 63/483,075 filed on 02/03/2023 under 35 U.S.C. 119(e). The examiner finds support for all claimed limitations in the provisional applications; therefore, the pending claims are being examined with an effective filing date of 04/06/2022.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/27/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 78 is objected to because of the following informalities: line 2 of alternative limitation “e)” recites “the the,” which is a duplicate typo. Appropriate correction is required.
Claim Interpretation
Claims 2, 19, 23, 62, 69, 78, 124, and 129 recite alternative claim limitations using “or” or “and/or;” the examiner has considered only one from the lists in the alternative as being required, However, for compact prosecution and customer service, the examiner considered more than one alternative limitations as applicable to cited prior art rejections.
Claim 2 recites “optionally wherein” for alternative limitation “c)” and “f).” The examiner is not considering limitation that follow “optionally wherein” as being required; thus, such limitations will not be considered to further limit the claim and the broadest reasonable interpretation will be afforded based on the preceding limitation listed in the alternative. However, for compact prosecution and customer service, the examiner will consider as many of the optional limitations as possible with respect to the prior art.
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 23, 86, and 89 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 23 recites “one or more Byrne enhancer elements and/or one or more Paulin enhancer elements,” and claims 86 and 89 recite “a Byrne desmin enhancer element” and “a Paulin desmin enhancer element.” However, the specification fails to provide a clear structural and/or functional distinction between these two elements, leading to “insoluble ambiguity” regarding the metes and bounds of the claims. Specifically, SEQ ID NO: 21 is provided as an example of the “Byrne enhance” and SEQ ID NO: 22 is provided as an example of the “Paulin enhancer.” However, unlike the Byrne enhancer, the Paulin enhancer is defined by the applicant’s citation of Li and Paulin’s NPL and by genomic positions upstream of the Desmin coding region. Furthermore, a sequence comparison reveals that the 277 bp Paulin enhancer is a direct sub-sequence of the 359 bp Byrne enhancer (aligning, for example, to n=bases 21-297). exhibit significant overlap. It appears that the “Byrne enhancer” sequence, differing only by the inclusion of additional upstream nucleotides. While the term “Paulin enhancer” has recognized meaning in the gene regulation field based on the cited Li and Paulin NPL, the term “Byrne enhancer” does not appear to be a term of the art. Because the “Byrne” sequence is merely an extension of “Paulin” sequence, it is unclear whether these terms are intended to represent: (a) two distinct, independent regulatory elements; (b) overlapping fragments of the same regulatory region; or (C) synonymous terms for the same genetic locus.
A person of ordinary skill in the art would not be able to determine the metes and bounds of the claim when selecting between these alternatives for the following reasons: (a) lack of mutual exclusivity because the Byrne enhancer entirely encompasses the Paulin enhancer, the use of the “and/or” connector creates a situation where a single physical sequence (the 359 bp Byrne enhancer) could simultaneously satisfy both alternatives. It is unclear if a construct containing the 359 bp sequence is intended to be “one Byrne enhancer,” “one Paulin enhancer plus additional nucleotides,” or “one of each.” (b) No objective standard for differentiation because the specification provides no standard or functional characteristic to distinguish the Byrne enhancer from the Paulin enhancer sequences other than a minor difference in length of two example sequences. Given that the field recognizes the “Paulin enhance” as the source of this regulatory activity, the use of a second, non-standard term (“Byrne enhancer”) to describe a slightly longer fragment of the same locus fails to provide the requisite degree of clarity. (c) ambiguous boundaries because it is unclear whether a sequence that is longer than the 277 np Paulin core but shorter than the 359 bp Byrne fragment would be classifies as one, the other, or neither. Without clear definitions of where the Byrne enhancer ends and the paulin identity begins, the public
Claim 125 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 125 depends from claim 124 and recites “the RNA linker comprises from about 4 to about 50 nucleotides. However, the parent claim 124 specifically limits the RNA linker to “SEQ ID NO: 3 or with a sequence with about 90% identity to the sequence of SEQ ID NO: 3.” SEQ ID NO: 3 consist of 19 nucleotides. A sequence with about 90% identity to a 19-mer is structurally constrained to a length approximately equal to the reference sequence (within 1-2 bases or 17-21 nucleotides.) A conflict exists between the limitations of the parent claim 124 and dependent claim 125 for the following reasons: (a) direct contradiction of scop because claim 125 purports to further limit the parent claim but instead introduces a range (bout 4 to about 50 nucleotides) that significantly broadens and contradicts the narrow structural constraint of the parent claim (the 19-mer of SEQ ID NO:3). A person of ordinary skill in the art would not be able to determine the metes and bounds of the invention when a dependent claim permits a length that is mathematically and structurally excluded by the parent clam’s 90% identity requirement. (2) improper dependency because it is a fundamental principal of claim construction that a dependent claim must further limit the scope of the parent claim. Here, claim 125 introduces a range that is inconsistent with the specific sequence requirement of claim 124. This inconsistency renders the scope of the claim unclear, as it is impossible to determine if the linker must adhere to the specific sequence identity of SEQ ID NO: 3 or if it may be any arbitrary sequence within the about 4 to about 50 nucleotides range.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 76 is rejected under 35 U.S.C. 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. 101).
Claim 79 recites “a cell comprising the expression cassette of claim 23.” The specification does not provide any guidance as to the meaning of the term “a cell,” nor does the claim limit to a particular type of cell. Since the cell recited in claim 1 comprises a vector that is intended to be administered to a subject for treating a disease, the cell in claim 76 is interpreted to be present in a human. Therefore, a cell of claim 79 when present in vivo, reads on a human organism, which is excluded from the scope of patentable subject matter under 35 U.S.C. 101 and section 33(a) of the America Invents Act. Applicant is advised to amend such that the claim recites “an isolated cell.”
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Geall et. al., (US 20190298847 A1, in IDS).
Claim 1, is directed to an RNAi molecule comprising a first strand and a second strand forming a duplex, wherein the first strand (guide) comprises SEQ ID NO: 1 and the second strand comprises a non-guide region. The examiner notes that the use of the open-ended transition “comprising” means the claim is to include any molecule that contains the recited 21-mer sequence, even if additional nucleotides are present.
Regarding claims 1-2 and 19, Geall teaches “polynucleic acid molecules, pharmaceutical compositions, and methods for treating muscle atrophy or myotonic dystrophy,” see abstract. Geall teaches a systematic “walking” library of polynucleic acid molecules designed to target the DMPK gene via RNA interference (RNAi). Geall teaches RNAi polynucleic acid molecules that target sequences set forth in SEQ ID NOs: 28-141, 370-480, or 703-3406, of which SEQ ID NOs: 2646-2648 are of particular relevance to the claimed SEQ ID NO: 1 in the instant case. SEQ ID NOs: 2646-2648 are 23-mer “target RNA” sequences, see claims 1 and 8 and [0118-0120]. In the field of RNAi and as taught by Geall, “the sense strand comprises nucleotide sequence corresponding to the target nucleic acid sequence or a portion thereof” (see [0186]). Therefore, a disclosure of a “target RNA” sequence is a disclosure of the sense/passenger strand of an RNAi. Because the 23-mers taught by Geall are 100% identical to the passenger-side complement of the claimed 21-mer of SEQ ID NO: 1, Geall’s disclosure of SEQ ID NOs: 2646-2648 anticipate the claimed RNAi guide sequence.
Geall explicitly teaches that the RNAi polynucleic acid comprises a sense strand (passenger) and an antisense (guide) strand, see [0126]. Geall further teaches that the sense and antisense strands are complimentary to one another and form a duplex (see [0186-0189]), and considering the well-established principle of Watson-Crick base pairing, the disclosure of a sense strand inherently discloses its complementary antisense strand. The antisense compliment of Geall’s SEQ ID NO: 2646-2648 is a 23-mer that contains the 21-nucleotide sequence of the claimed SEQ ID NO: 1 with 100% identity, see sequence results attached to the file wrapper. Under the “comprising” construction of the claim, the 23-mer antisense strand anticipates the claimed 21-mer guide sequence.
While the specific sequences cited above (2646-2648) are 23-mers, Geall provided a robust framework of overlapping length ranges that encompass the claimed 21-mer. Geall teaches, for example, that the molecules can be: “about 18 to about 25 nucleotides…about 19 to about 23 nucleotides…about 20 to about 22 nucleotides,” see [0124-0130]. A 21-mer falls squarely within these narrowly defined, nested ranges.
Furthermore, Geall teaches SEQ ID NO: 13,462, which is a 19-mer specifically categorized as an antisense/guide strand, see [0121]. This 19-mer is 100% identical to the first 19 nucleotide bases of the claimed SEQ ID NO: 1. Having 19 bases identical to the 21-mer sequence claimed provides a 90.4% identity, which falls within the claimed about 90% identity structural limitation.
Geall does not merely disclose a random list of sequences, rather Geall teaches: (1) the specific DMPK genetic targets; (2) the specific sequences (e.g., SEQ ID NOs: 2646-2648); and (3) the specific architecture and length (i.e., duplex comprising a 20-22 nucleotide antisense strand). Because Geall provides a 100% sequence match within a disclosed range of “about 20 to about 22” nucleotides for the purpose of targeting the same gene (DMPK), the prior art is in possession of the claimed invention.
Further regarding claim 2, Geall teaches the first strand and the second strand are linked by means of an RNA linker capable of forming a loop structure ([0167]: “the sense strand is connected to the antisense strand via a linker molecule, which … is a polynucleotide linker”). Geall teaches the RNAi is a small inhibitory RNA (siRNA), a microRNA (miRNA), or a small hairpin RNA (shRNA) ([0123]: “the polynucleic acid molecule comprises RNA…RNA comprises short interfering RNA (siRNA), short hairpin RNA (shRNA), microRNA (miRNA)…”). Geall further teaches “an asymmetric hairpin is a linear polynucleic acid molecule comprising an antisense region, a loop portion that comprises nucleotides or non-nucleotides, and a sense region that comprises fewer nucleotides than the antisense region to the extent that the sense region has enough complimentary nucleotides to base pair with the antisense region and form a duplex with loop. For example, an asymmetric hairpin polynucleic acid molecule comprises an antisense region having length sufficient to mediate RNAi in a cell or in vitro system (e.g. about 19 to about 22 nucleotides) and a loop region comprising about 4 to about 8 nucleotides, and a sense region having about 3 to about 18 nucleotides that are complementary to the antisense region.” See [0188].
Further regarding claim 19, Geall teaches “a polynucleic acid molecule that hybridizes to a target sequence of human DMPK and mediates RNA interference against the human DMPK” see claim 1, and that “mediation of RNA interference against the human DMPK modulates muscle atrophy or myotonic dystrophy in a subject” see claim 3. Geall further teaches “the myotonic dystrophy is DM1” see [0008], and that “DM1 is caused by a dominantly inherited “CTG” repeat expansion in the gene DM protein kinase (DMPK),” see [0310]. Geall teaches the polynucleic acid molecules comprising the RNAi may be delivered by a recombinant vector, which may be a viral vector “derived from adeno-associated virus, retrovirus, adenovirus, or alphavirus,” see [0345].
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 1-2, 19, 23 and 76 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et. al., (US 20190298847 A1, in IDS) in view of Williams (WO 2022056291 A1, published 03/17/2022, priority to US18/181,796 with effective filing date 09/11/2020) and Souza et. al., (US 20030100526 A1).
The teaching of Geall are incorporated herein by reference to the 102 rejection above.
Geall does not teach: an expression cassette comprising nucleic acid encoding an RNAi targeting DMPK, wherein the nucleic acid encoding the RNAi is operably linked to a desmin promoter wherein the desmin promoter: a) comprises two enhancer elements and the promoter for the human desmin gene; b) comprises one or more Byrne enhancer elements and/or one or more Paulin enhancer elements; c) comprises one or more enhancer elements comprising the nucleotide sequence of SEQ ID NO: 21 or a nucleotide sequence with about 90% identity to the sequence of SEQ ID NO:21 and/or one or more enhancer elements comprising the nucleotide sequence of SEQ ID NO:22 or a nucleotide sequence with about 90% identity to the sequence of SEQ ID NO:22; or d) comprises the nucleotide sequence of SEQ ID NO:12 or a sequence with about 90% identity to the nucleotide sequence of SEQ ID NO:12.
Williams teaches “novel combinations of muscle-specific enhancers and promoters useful for achieving high and persistent expression in muscle tissue or myocytes,” see abstract. Williams further teaches “combining desmin muscle-specific promoters and desmin muscle-specific enhancers and MCK muscle-specific enhancers to provide hybrid promoters that drive transgene expression in muscle cells and tissues,” and that “the resulting hybrid promoters are useful for muscle cell and gene therapy,” see [0012]. Williams further teaches “a mammalian desmin promoter, a mammalian desmin enhancer, and one or more mammalian muscle creatine kinase (MCK) enhancers that are operably linked,” see [0013] and as in claim 1. Williams further teaches that “the mammalian desmin promoter is human, the mammalian desmin promoter can include a nucleic acid sequence having 80% or more identity to any of SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, and SEQ ID NO: 10,” see claims 1-4 and [0066].
Williams further teaches additional elements such as “an intron can be inserted in the muscle-specific regulatory nucleic acid sequence” and that the “transgene can be positioned downstream from the mammalian desmin promoter, possibly between the additional elements…,” see [0098]. Wilson further teaches the use of the “Bovine Growth Hormone derived polyadenylation signal” element, see [0126].
Williams further teaches “the mammalian desmin enhancer comprises a nucleic acid sequence having at least 80% identity to the nucleic acid sequence of SEQ ID NO: 6,” see claims 9-10, which aligns with a 100% identity score to claimed SEQ ID NO: 22 of the instant case. Williams further teaches SEQ ID NO: 50, as the “Human Desmin Enhancer (hdesmin (-1008 to -558) enhancer),” which comprises the claimed SEQ ID NO: 21 with a 99.6% identity score (see Table 2 [0120] and sequence search results attached to the file wrapper). Wilson further teaches that “it should also be understood that there can be multiple mammalian desmin enhancers and that any combination of the mammalian desmin enhancer(s)…can be made in terms of the order of the elements,” see [0098], and that the Desmin enhancers can be 5’ to the Desmin promoter, see [0134]. Thus, when assembling the Desmin enhancer elements defined as SEQ ID NOs: 50 and 6 with the Desmin promoter element defined by SEQ ID NO: 9 taught by Williams, in the following order, SEQ ID NO: 50, SEQ ID NO: 6, and SEQ ID NO: 9, a Desmin enhancer/promoter sequence is assembled with a 97.4% identity score to claimed SEQ ID NO: 12 in the instant case, which meets the about 90% identity requirement claimed. See sequence alignment below:
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424
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Williams further teaches that “the various muscle-specific hybrid promoters … may be used for muscle-specific transgene expression in cultured cells or tissues from, by way of example but not limitation, episomal or integrated plasmid, Nanoplasmid, minicircle, Doggybone, MIDGE, adenoviral, adeno-associated viral (AAV), retroviral, and lentiviral vectors, see [0012][0101][0126].
Souza teaches “a regulatory element comprises at least two desmin (DES) enhancers linked to a DES promoter,” see [0014]. Souza further teaches “A 280-bp enhancer located between nt −973 and −693 of the human sequence contains several sequences homologous to other muscle-specific enhancers. Unlike other muscle-specific enhancers, the desmin (DES) enhancer can function in myoblasts as well as myotubes. The DES enhancer contains two different regions, one is active in differentiated myotubes, between nt −973 and −848, the other is active in undifferentiated myoblasts, between nt −847 and −693. Deletion of the region between nt −1738 and −693 results in a more than 20-fold decrease in expression of a linked CAT gene in differentiated muscle cells and 8-fold decrease in undifferentiated myoblasts. This 280-bp enhancer is independent of orientation, position, and distance, and can activate either the desmin promoter or heterologous promoters, such as HSV tk and human vimentin, at about 14- to 50-fold in C2.7 myotubes, and 9- to 16-fold in C2.7 myoblasts,” see [0040]. Souza further teaches “the sequence of human muscle-specific 243 bp DES enhancer (-973 to −731) is provided in SEQ ID NO:21,” see [0041] and claim 9.
Souza further teaches that “a regulatory element comprises at least two DES enhancers linked to a DES promoter” see [0014], and that a regulatory element/sequence is defined as “promoters, enhancers, and other expression control elements, or any combination of such elements,” see [0028].
Souza further teaches that “a human desmin (DES) promoter was obtained by cloning of the 5′ flanking region from nt −2194 to +1 into pCR-Blunt II-TOPO” see [0038], and that “the sequence of the truncated DES promoter is provided in SEQ ID NO:19,” see [0039].
Souza further teaches that the regulatory elements may be “ incorporated into a viral vector such as one derived from adenoviruses, adeno-associated viruses (AAV), or retroviruses, including lentiviruses such as the human immunodeficiency (HIV) virus,” which are useful for “ transfecting muscle tissue,” see [0015]. Souza further teaches “a transfected host cell comprising the vector,” see claims 27-30.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to operably link the RNAi of Geall to the desmin enhancer(s)/promoter(s) taught by Williams, as further supported by Souza.
Geall teaches RNAi molecules targeting DMPK for modulation of myotonic dystrophy but does not specify a particular promoter and enhancer elements for expression, rather Geall uses antibody conjugate for targeting. Williams teaches muscle-specific regulatory nucleic acid sequences comprising a mammalian/human desmin promoter and desmin enhancer elements operably linked to drive transgene expression in muscle cells. Williams further teaches that combinations of desmin enhancer elements may be used and arranged in various configurations. Souza teaches that regulatory elements comprising at least two desmin enhancers linked to a desmin promoter provide robust transcriptional activation in muscle cells/tissue, and that the desmin enhancer contains two different functional regions active in either differentiated myotubes or undifferentiated myoblasts.
A PHOSITA would have been motivated to place the RNAi of Geall under transcriptional control of the desmin enhancer/promoter combinations of Williams and Souza in order to achieve muscle-specific expression of the RNAi construct. The combination merely involves linking a known RNAi payload to a known muscle-specific regulatory element for expression in muscle cells/tissue, representing the predictable use of prior art elements according to their established functions. A PHOSITA would have had a reasonable expectation of success because the references teach modular expression constructs in which promoters and enhancers are operably linked to heterologous nucleic acids sequences, and the desmin regulatory elements of Williams and Souza are explicitly taught to drive expression of downstream transgenes.
It would have further been obvious to a PHOSITA to transfect cells with the above expression cassette, thereby generating cells comprising the expression cassette because introducing expression constructs into cells to obtain cells expressing encoded components was a routine and conventional step as taught by both Williams and Souza. A PHOSITA would have had a reasonable expectation of success because both Williams and Souza report the desmin enhancer/promoter expression cassettes robustly and stably express transgenes in muscle cells/tissue without deleterious effects.
Claims 62, 69, 78, 92, 124-130 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et. al., (US 20190298847 A1, in IDS) in view of Williams (WO 2022056291 A1, published 03/17/2022, priority to US18/181,796 with effective filing date 09/11/2020) and Souza et. al., (US 20030100526 A1) as applied to claims 1-2, 19, 23, and 76 above, and further in view of Hou et. al., (US 20200377887 A1), O'Riordan (US 20170173183 A1), and Yao (US 20200172928 A1).
Regarding claim 92, Geall further teaches “a pharmaceutical composition comprising: a molecule described above or a polynucleic acid molecule conjugate described above; and a pharmaceutically acceptable excipient,” see [0007].
Neither Geall, Williams, nor Souza explicitly teaches the specific stuffer positions and sequences derived from SERPINA1, the specific rAAV vector architectures (ITRs/Capsids/scAAV), rabbit β-globin intron, or the miR-155 scaffolded RNAi structural linkers and orientations. However, these features were well-known and routine in the art of rAAV vector design for gene therapy.
Regarding the stuffer sequence (SERPINA1/A1AT) limitations:
Hou teaches “the viral genome comprises one or more filler sequences in order to have the length of the viral genome be the optimal size for packaging,” and that “ in order to have the length of the viral genome be about 4.6 kb.,” see [0178]. Hou further teaches “the viral genome comprises two filler sequences, and the first filler sequence is located 3′ to the 5′ ITR sequence and the second filler sequence is located 3′ to the polyadenylation signal sequence,” see [0183]; “the filler sequence is located 5′ to the 3′ ITR sequence,” see [0184]; and “a filler sequence may be located between two regions, such as …the polyadenylation signal sequence region and the 3′ ITR,” see [0196]. Hou further teaches that “ the vectors with a 5′ or 3′ filler sequence vectors presented the highest titers,” see [0665]. Hou further teaches SEQ ID NOs: 45, 62, and 64, which are defined as respectively: (45) construct HT106 ITR to ITR sequence (see [0351]); (62) Filler002 (see [0357]); and (64) Filler004 (see [0357]. Each of these three sequences align to SEQ ID NO: 18 of the instant case with 92.4% identity score, thereby salifying the claimed “with about 90% identity to the sequence of SEQ ID NO: 18” limitation. Hou further teaches SEQ ID NOs: 45, 49, 62, and 66, which are defined as respectively: (45) construct HT106 ITR to ITR sequence (see [0351]); (49) construct HT110 ITR to ITR sequence (see [0351]); (62) Filler002 (see [0357]); and (65) Filler005 (see [0357]. Each of these four sequences align to SEQ ID NO: 19 of the instant case with 96.7% identity score, thereby satisfying the claimed “with about 90% identity to the sequence of SEQ ID NO: 19” limitation. Furthermore, Hou teaches SEQ ID NOs: 46 and 63, which are defined as respectively: (46) construct HT107 ITR to ITR sequence (see [0351]) and (63) Filler003 (see [0357]). Each of these two sequences align to SEQ ID NO: 19 of the instant case with 95.5% identity score, thereby salifying the claimed “with about 90% identity to the sequence of SEQ ID NO: 19” limitation. Hou teaches “the AAV particle viral genome comprises at least one filler sequence region,” see [0360].
O'Riordan teaches rAAV vectors with two stuffer sequences, one positioned 3’ to the 5’ ITR and the other positioned 3’ to the BGH PolyA and 5’ to the 3’ ATR. For example, O'Riordan teaches “the nucleic acid in the AAV comprises 5′ to 3′ nucleic acid encoding the following: an AAV ITR, a stuffer fragment (e.g., SEQ ID NO:11), an RK promoter, a chimeric intron (e.g., SEQ ID NO:10), a human rhodopsin, a β-globin intron, a miR-708 embedded in a β-globin intron, a bovine growth hormone polyadenylation sequence, a stuffer fragment, and an AAV ITR,” see [0121].
Regarding the recombinant adeno-associated virus (rAAV) vector limitations:
Hou teaches that the “…modulatory polynucleotides encoding the RNAi molecules may be inserted into recombinant AAV vectors,” see [0003]. Hou further teaches “the AAV particles…comprise a viral genome with at least one ITR region and a payload region,” or that “the viral genome has two ITRs,” wherein “these two ITRs flank the payload region at the 5′ and 3′ ends,” see [0081]. Hou further teaches that “the AAV serotype may be, but is not limited to” AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, etc., see [0058]. Hou further teaches self-complementary AAV viral genomes (scAAVs)…contain DNA strands which anneal together to form double stranded DNA.,” and “by skipping second strand synthesis, scAAVs allow for rapid expression in the cell,” see [0051]. Hou further teaches “a cell comprising an AAV polynucleotide and/or AAV genome,” see [0389].
O'Riordan teaches rAAV vectors wherein “the AAV vector comprises an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV2R471A, AAV DJ, a goat AAV, bovine AAV, or mouse AAV serotype ITR,” see [0014]. O'Riordan further teaches and claims the AAV ITRs are AAV2 ITRs, see [0015] and claims 46 and 49-50. O'Riordan further teaches “self-Complementary AAV Viral Genomes,” see [0123].
Regarding the recombinant AAV particle/capsid and composition comprising limitations:
Hou teaches “an AAV capsid selected from” the same list above as the serotypes above, see [0058]. Hou further teaches “the ITRs may be derived from the same serotype as the capsid,” see [0082]. Hou further teaches “the ITR may be of a different serotype from the capsid,” see [0082]. Hou teaches “a pharmaceutical composition comprising the AAV particle,” see claim 11.
O'Riordan teaches “the AAV viral particle comprises an AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAVrh8, AAVrh8R, AAV9, AAV10, AAVrh10, AAV11, AAV12, AAV2R471A, AAV2/2-7m8, AAV DJ, AAV2 N587A, AAV2 E548A, AAV2 N708A, AAV V708K, a goat AAV, AAV1/AAV2 chimeric, bovine AAV, or mouse AAV capsid rAAV2/HBoV1 serotype capsid,” see [0012]. O'Riordan further teaches “the ITR and the capsid of the rAAV viral particles are derived from different AAV serotypes,” see claim 48, and “the ITR and the capsid of the rAAV viral particle are derived from the same AAV serotype,” see claim 47. O'Riordan further teaches that “the rAAV viral particles are in a pharmaceutical composition,” and “the pharmaceutical composition further comprises a pharmaceutically acceptable carrier,” see [0019]. O'Riordan further teaches “a cell comprising the nucleic acid, the expression construct, or the vector,” see [0034].
Regarding the miRNA scaffold, RNA linker, and orientation limitations:
Hou teaches “an adeno-associated virus (AAV) viral genome, comprising: a) a 5′ inverted terminal repeat (ITR) sequence region…; b) an enhancer sequence region…; c) a promoter sequence region…; d) a modulatory polynucleotide sequence region…; e) a polyadenylation (polyA) signal sequence region…; and f) a 3′ ITR sequence region…” see claim 1. Hou further teaches that “a “modulatory polynucleotide” is any nucleic acid sequence(s) which functions to modulate (either increase or decrease) the level or amount of a target gene, e.g., mRNA or protein levels,” see [0205]. Hou further teaches that “at least one siRNA, miRNA or other RNAi agent described herein, may be encoded by a modulatory polynucleotide which may also comprise at least one molecular scaffold,” see [0300]. Hou further teaches methods of designing the modulatory polynucleotides encoding novel double stranded RNAi constructs, see [0008]. Hou further teaches that a “modulatory polynucleotide comprises in the 5′ to 3′ direction, a 5′ flanking sequence, a 5′ arm, a loop motif, a 3′ arm and a 3′ flanking sequence,” and that “ the 5′ arm may comprise a nucleic acid sequence encoding a sense sequence and the 3′ arm comprises a nucleic acid sequence encoding the antisense sequence” or “the 5′ arm comprises a nucleic acid sequence encoding the antisense sequence and the 3′ arm comprises a nucleic acid sequence encoding the sense sequence,” see [0314]. Hou further teaches that Hou further teaches “separating the sense and antisense sequence of the stem loop structure of the modulatory polynucleotide is a loop sequence (also known as a loop motif, linker or linker motif). The loop sequence may be of any length, between 4-30 nucleotides, between 4-20 nucleotides, between 4-15 nucleotides, between 5-15 nucleotides, between 6-12 nucleotides, 6 nucleotides, 7 nucleotides, 8 nucleotides, 9 nucleotides, 10 nucleotides, 11 nucleotides, 12 nucleotides, 13 nucleotides, 14 nucleotides, and/or 15 nucleotides,” see [0307]. Hou further teaches the use miR155 scaffold, see [0209][0211][0342]. Hou further teaches that “ the 5′ arm, sense and/or antisense sequence, loop motif and/or 3′ arm sequence may be altered (e.g., substituting 1 or more nucleotides, adding nucleotides and/or deleting nucleotides). The alteration may cause a beneficial change in the function of the construct (e.g., increase knock-down of the target sequence, reduce degradation of the construct, reduce off target effect, increase efficiency of the payload, and reduce degradation of the payload),” see [0315]. Hou further teaches SEQ ID NO: 12 corresponding to a 5’ miR155 scaffold portion, which aligns with 100% identity to SEQ ID NO: 9 of the instant case. Hou further teaches SEQ ID NO: 21 corresponding to a 3’ miR155 scaffold portion, which aligns with 100% identity to SEQ ID NO: 10 of the instant case. Hou further teaches SEQ ID NO: 17 corresponding to a miR155 loop structure, which aligns with 100% identity to SEQ ID NO: 3 of the instant case. See sequence search results attached to the file wrapper.
O'Riordan teaches the use of a miR155 scaffold, see [0008][0023]. O'Riordan further teaches the miRNA containing the loop/linker sequence was “cloned between 5′ and 3′ miR-155 scaffold sequence,” see [0038]. O'Riordan further teaches “The miR-155 “loop sequence” between the 5′ and 3′ miR flanking sequences is labeled in FIG. 23C,” see [0058]. O'Riordan further teaches “the miR-155 scaffold is provided by SEQ ID NO:14,” see [0118]. O'Riordan further teaches “this scaffold sequence contains the target sites required for Drosha to process pri-miR-708 into pre-miR-708 in the nucleus, allowing subsequent processing of pre-miR-708 by Dicer in the cytoplasm,” see [0038]. O'Riordan further teaches “that the miR-155 flanking sequences generate better expression (or miRNA processing) of miR-708 compared to endogenous miR-708 flanking sequences,” and that “miR-708 expression was about 10-fold higher in those cells transfected with vectors containing the miR-155 flanking sequences compared to miR-708 flanking sequences,” see [0174].
Regarding additional elements: rabbit β-globin intron and PolyA signal limitations:
Hou further teaches “the nucleic acid sequence comprising the payload region may comprise one or more of a promoter region, an intron, a Kozak sequence, an enhancer or a polyadenylation sequence,” see [0039][0067-0069]. Hou further teaches “elements to enhance the transgene target specificity and expression include promoters, endogenous miRNAs, post-transcriptional regulatory elements (PREs), polyadenylation (PolyA) signal sequences and upstream enhancers (USEs), CMV enhancers and introns,” see [0086]. Hou further teaches “the viral genome comprises an enhancer element, a promoter and/or a 5′UTR intron,” see [0121]. Hou further teaches “the payload region comprises at least one element to enhance the expression such as one or more introns or portions thereof,” see [0166]. Hou further teaches the use of introns such as MVM (67-97 bps), FIX truncated intron 1 (300 bps), 0-globin SD/immunoglobulin heavy chain splice acceptor (250 bps), adenovirus splice donor/immunoglobin splice acceptor (500 bps), SV40 late splice donor/splice acceptor (19S/16S) (180 bps) and hybrid adenovirus splice donor/IgG splice acceptor (230 bps),” see [0166], or “others known in the art,” see [0179]. Hou also teaches the use of “a chimeric intron,” see [0174]. Hou further teaches the use of an “SV40…a human beta globin intron in an expression vector,” or “or others known in the art,” see [0161 and 0175]. Hou further teaches SEQ ID NO: 67 defined as a non-limiting example of PolyA sequence, which comprised with 100% identity score to SEQ ID NO: 16 of the instant case corresponding a BGH PolyA sequence or portion thereof.
O'Riordan teaches embedding nucleic acid sequences encoding miRNA constructs “in an intron,” see claim 24. O'Riordan further teaches miRNA “sequence embedded in the beta globin intron,” see [0184] and FIG. 23A. O'Riordan further teaches that “FIG. 24 shows the evaluation of candidate vectors harboring the miR-708 sequence, either in the miR-155 or the miR-708 scaffold (embedded in the beta-globin intron),” see [0059]. O'Riordan further teaches that such vectors comprising miRNA embedded in the beta globin intron “resulted in…expression in human cells in vivo, as compared to vectors driving expression of a control miR from either the opsin or the rhodopsin kinase promoter (Ops miR-Cont and RK miR-Cont, respectively),” and that “these results demonstrate the successful validation of several vectors that may be used for suppression/replacement strategies (such as those described above) in human cells,” see [0185].
Yao teaches the “beta-globin intron (SEQ ID NO: 10),” see [0099],F which aligns to the rabbit β-globin intron sequences, SEQ ID NO: 14 and SEQ ID NO: 15, of the instant case, with 89.5% and 100% identity score, respectively.
It would have been obvious to a person having ordinary skill in the art (PHOSITA) to further modify the DMPK-silencing expression cassette of Geall in view of Williams and Souza to include a miR-155 scaffold & linker, a 5′ and 3′ portion of a rabbit β-globin intron, and a BGH polyadenylation signal as taught by Hou, O’Riordan, and Yao, thereby arriving at a sequence having about 90% identity to SEQ ID NO: 17.
Hou teaches miR-155 scaffolded RNAi constructs comprising a 5′ scaffold sequence, a guide strand, a loop sequence, a passenger strand, and a 3′ scaffold sequence, and further teaches that these elements may be modified while maintaining function. O’Riordan teaches embedding miRNA constructs within a beta-globin intron, thereby generating a 5′ intron arm upstream of the embedded miRNA and a 3′ intron arm downstream of the embedded miRNA. Yao teaches the rabbit β-globin intron sequence, which aligns with the claimed 5′ and 3′ arms of the rabbit β-globin intron with 89.5% and 100% identity, respectively. Accordingly, embedding the miR-155 scaffolded DMPK-targeting RNAi of Geall within the rabbit β-globin intron taught by Yao, as taught by O’Riordan, results in a construct comprising a 5′ rabbit β-globin intron arm, the miR-155 scaffolded RNAi sequence, and a 3′ rabbit β-globin intron arm, driven by a desmin promoter with desmin enhancers and terminated by a BGH PolyA signal as recited. Specifically, Williams and Souza teach the desmin promoter/enhancer regulatory elements, Hou teaches the miR-155 scaffold and loop sequence portions, Geall teaches the DMPK-targeting guide sequence, Yao teaches the rabbit β-globin intron arms, and Hou further teaches the BGH polyadenylation signal. These elements collectively account for approximately 1,755 nucleotides of the 1,913 nucleotide SEQ ID NO: 17, corresponding to approximately 91.7% sequence identity. Because the claimed SEQ ID NO: 17 represents an assembly of known functional elements taught in the prior art, and it is largely in the identical configuration of rAAV miRNA vectors taught by O’Riordan, a PHOSITA would have found it obvious to combine these elements in the configuration of SEQ ID NO: 17.
It would have further been obvious to modify the expression cassette to include SERPINA1 stuffer sequences and recombinant AAV architecture elements (i.e., ITRs and Capsids) for rAAV vector and rAAV particle generation because such elements were well-known interchangeable components routinely used in rAAV vector design. Hou teaches the use of filler/stuffer sequences to increase vector genome size toward optimal AAV packaging capacity and to improve production of stable, high-titer rAAV particles. O’Riordan further teaches rAAV constructs comprising 5′ and 3′ stuffer sequences flanking an expression cassette, and ITR sequences capping off both the 5’ and 3’ ends of the vector, thereby teaching the claimed arrangement. It would have further been obvious to package the resulting rAAV vector into rAAV particles, and include the rAAV particles in a pharmaceutical composition because Hou and O’Riordan both teach compositions comprising rAAV particles packaged with rAAV vectors encoding RNAi constructs.
A PHOSITA would have been motivated to use the miR-155 scaffold and loop/linker sequence taught by Hou and O’Riordan because such scaffolds were taught to promote efficient Drosha/Dicer processing and reliable liberation of the guide strand for target transcript silencing. A PHOSITA would have further been motivated to incorporate the rabbit β-globin intron and BGH PolyA signal into the expression cassette design because such regulatory elements were conventionally included in rAAV expression cassettes to enhance transcript processing and expression efficiency. Furthermore, regarding the rabbit β-globin intron, a PHOSITA would have been motivated to embed the miR155 scaffold comprising the miRNA within the rabbit β-globin intron, generating a 5’ arm and 3’ arm, in order to ensure robust expression in human cells as demonstrated by O’Riordan. A PHOSITA would have further been be motivated to include the SERPINA1 (A1AT) stuffer taught by Hou to increase the vector genome size toward the optimal packaging capacity for rAAV vectors, as Hou teaches that such filler sequences are used to increase vector genome size and improve production of stable, high-titer rAAV particles. A PHOSITA would have further been motivated to utilize the self-complementary (scAAV) format taught by Hou and O'Riordan to bypass the rate-limiting step of second-strand synthesis and thereby achieve more rapid transgene expression.
A PHOSITA would have had a reasonable expectation of success because rAAV vectors are assembled using modular, functionally independent components, including AAV ITRs, stuffer sequences, miRNA scaffolds, introns, and polyadenylation signals, which were known to function predictably when combined with different RNAi payloads. Because Hou, O’Riordan, and Yao demonstrate successful use of these same elements in AAV-mediated RNAi constructs, a PHOSITA would have expected similar structural and functional results when applying these known components to the DMPK-targeting system of Geall in view of Williams and Souza. A PHOSITA would therefore have had a reasonable expectation of success in generating the claimed rAAV vector and a composition comprising rAAV particles packaged with the DMPK-targeting RNAi construct.
Claims 86, 88-89, and 92 are rejected under 35 U.S.C. 103 as being unpatentable over Geall et. al., (US 20190298847 A1, in IDS) in view of Williams (WO 2022056291 A1, published 03/17/2022, priority to US18/181,796 with effective filing date 09/11/2020) and Souza et. al., (US 20030100526 A1) as applied to claims 1-2, 19, 23, and 76 above, further in view of Hou et. al., (US 20200377887 A1), O'Riordan (US 20170173183 A1) and Yao (US 20200172928 A1) as applied to claims 62, 69, 78, 92, 124-130 above, and in further view of Loiler (WO2020047472A1) and Wahbi et. al., (Trends Cardiovasc Med. 2020 May; 30(4):232-238).
While Hou and O'Riordan teach the use of a variety of AAV capsid serotypes, none of the above references teach the following mutant capsids: AAVrh74 N502I capsid and its corresponding SEQ ID NO: 50, and AAVrh74 W505R capsid and its corresponding SEQ ID NO: 52.
Loiler teaches “Non- limiting examples of recombinant AAV backbones to create the vector include AAV vector serotypes from the group of AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV 10, AAV11, AAV 12, AAV13, AAV PHP.B, or AAV rh74. In a further aspect, the vector backbone is an AAV9 serotype, an AAVrh74 serotype, or a modified AAVrh74 serotype. Also provided is a polynucleotide encoding a modified AAVrh74 VP1 capsid protein comprising one or more modifications selected from the group of a substitution of isoleucine for asparagine at amino acid position 502, and an optional substitution of tryptophan to arginine at amino acid 505 of the VP1 of AAVrh74…” see [0008].
Loiler teaches that “one of the mutants (AAVmut4, asparagine to lsoleucine at amino acid 502 of VP1 capsid) increases gene delivery globally to all tissues tested up to 56-fold (between 3 and 56-fold increase depending on tissue) higher transduction efficiency,” see [0135][0137]. Loiler further teaches “AAV rh74 Consensus Sequence Alignment vs. AAVrh74 vs. AAVrh74-N502I-capsid vs. Rh74 YIG591 cap protein,” see “AAV rh74 Consensus Sequence Alignment” pages 55-56. Loiler further teaches SEQ ID NO: 11, which when aligning SEQ ID NO:50 of the instant case to SEQ ID NO: 11 of Loiter, there is 100% homology. See pages 55-56, [0135][0137], and sequence search results attached to the file wrapper.
Loiler teaches that “another mutant (AAVmut5, tryptophan to arginine at amino acid 505 of VP1 capsid) increases gene delivery to the heart almost 50-fold over AAVrh74,” see [0135]. Loiler teaches “AAV rh74 Consensus Sequence Alignment vs. AAVrh74 vs. AAVrh74-N502I-capsid vs. Rh74 YIG591 cap protein” see paged 55-56. When comparing SEQ ID NO:52 to the alignment of wild-type AAVrh74 taught by Loiter, there is a single amino acid difference, tryptophan to arginine substitution at position 505, which Loiler explicitly teaches as another mutant that exemplified enhanced gene delivery to the heart. SEQ ID NO: 52 is arrived at with 100% identity by applying the tryptophan to arginine substitution to the wild-type AAVrh74. See pages 55-56 and [0135][1037].
Wahbi teaches “patients with myotonic dystrophy, the most common neuromuscular dystrophy in adults, have a high prevalence of arrhythmic complications with increased cardiovascular mortality and high risk for sudden death,” see abstract.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the rAAV particle comprising the DMPK-targeting expression cassette of Geall in view of Williams, Souza, Hou, O'Riordan, and Yao to utilize a modified AAVrh74 capsid comprising the N502I substitution or the W505R substitution, as taught by Loiler, including capsids corresponding to SEQ ID NO: 50 and SEQ ID NO: 52. One of ordinary skill in the art would have been motivated because Loiler explicitly teaches that substitution of isoleucine for asparagine at position 502 of the AAVrh74 VP1 capsid increases gene delivery globally to tissues by up to 56-fold and that substitution of tryptophan to arginine at position 505 increases gene delivery to the heart by nearly 50-fold, thereby identifying these mutations as advantageous capsid modifications for enhancing in vivo transduction efficiency, particularly in muscle and cardiac tissues relevant to treatment of DMPK-associated myotonic dystrophy as further supported by Wahbi describing the cardiac involvement in DM1. One would have had a reasonable expectation of success because Loiler demonstrates successful generation and functional use of these specific AAVrh74 mutant capsids and teaches that such modified capsids can be used with conventional rAAV vector genomes, and Hou and O'Riordan teach that rAAV genomes may be packaged into a variety of interchangeable AAV capsid serotypes, indicating that substitution of one known functional capsid variant for another would have predictably resulted in an rAAV particle capable of delivering the DMPK-targeting expression cassette.
Double Patenting
STATUTORY (35 USC 101)
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
A statutory type (35 U.S.C. 101) double patenting rejection can be overcome by canceling or amending the claims that are directed to the same invention so they are no longer coextensive in scope. The filing of a terminal disclaimer cannot overcome a double patenting rejection based upon 35 U.S.C. 101.
Claims 86, 88-89, and 91 provisionally rejected under 35 U.S.C. 101 as claiming the same invention as that of claims 85, 87-88, and 90 of copending Application No. 18/626,784 (reference application). This is a provisional statutory double patenting rejection since the claims directed to the same invention have not in fact been patented.
Instant claim 86 is identical in scope to claim 85 of the reference application, as both claims recite an rAAV particle comprising an rAAV vector having the same ordered nucleic acid elements (AAV2 ITR, serpinA1 stuffer, Byrne desmin enhancer, Paulin desmin enhancer, desmin promoter, 5′ arm of rabbit β-globin intron, 5′ miR155 scaffold, DMPK204 guide, miR155 loop, DMPK204 passenger, 3′ miR155 scaffold, 3′ arm of rabbit β-globin intron, minimal BGH polyA, serpinA1 stuffer, AAV2 ITR) and further reciting the same AAVrh74 N502I capsid. Accordingly, instant claim 86 and reference claim 85 are drawn to identical subject matter.
Instant claim 88 depends from claim 86 and recites that the AAVrh74 N502I capsid comprises capsid proteins comprising the amino acid sequence of SEQ ID NO:50. Reference claim 87 depends from claim 85 and recites the identical limitation. Thus, instant claim 88 and reference claim 87 are drawn to identical subject matter.
Instant claim 89 is identical in scope to reference claim 88, as both claims recite the same rAAV vector architecture and further recite that the capsid is an AAVrh74 W505R capsid. Therefore, instant claim 89 and reference claim 88 are drawn to identical subject matter.
Instant claim 91 depends from claim 89 and recites that the AAVrh74 W505R capsid comprises capsid proteins comprising the amino acid sequence of SEQ ID NO:52. Reference claim 90 depends from claim 88 and recites the identical limitation. Accordingly, instant claim 91 and reference claim 90 are drawn to identical subject matter.
NON-STATUTORY
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 86 and 89 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 86 and 89 of copending Application No. 18/626,784 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claims 86 and 89 of the refence application recite an rAAV particle comprising the same ordered nucleic acid elements defined by SEQ ID NOs, including the same ordered nucleic acid elements (AAV2 ITR, serpinA1 stuffer, Byrne desmin enhancer, Paulin desmin enhancer, desmin promoter, 5′ arm of rabbit β-globin intron, 5′ miR155 scaffold, DMPK204 guide, miR155 loop, DMPK204 passenger, 3′ miR155 scaffold, 3′ arm of rabbit β-globin intron, minimal BGH polyA, serpinA1 stuffer, AAV2 ITR) and further reciting the same AAVrh74 N502I and AAVrh74 W505R capsids, respectively. The reference claims are narrower in that they explicitly recite the specific SEQ ID NOs for each element, whereas instant claims 86 and 89 generally recite the same structural components. Thus, the subject matter of the instant claims 86 and 89 are anticipated by claims 86 and 89 of the reference application, and the differences between the claims do not render the instant claims patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
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/COREY LANE BRETZ/ Patent Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
Prosecution Insights