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 and Claim Status Summary
Claims 48- 50, 62, 70, 71, 83, 92, 94, and 170- 177 are pending.
Claims 48- 50, 62, 70, 71, 83, 92, 94, and 170- 177 are considered on the merits.
Claims 48- 50, 62, 70, 71, 83, 92, 94, and 170- 177 are rejected.
No Claims are allowed.
This action is written in response to applicant's correspondence received 2026 July 24. Claims 48- 50, 62, 70, 71, 83, 92, 94, and 170- 177 are currently pending and under examination.
Election/Restrictions
Applicant’s election without traverse of invention Group II "method of using NA
Composition” in the reply filed on 2026 July 24 is acknowledged. Furthermore, the applicant’s concomitant cancellation of claims 1, 20, 22, 23, 25, 26, 31, 33, 35, 45, and 47 is acknowledged.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
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.
Claim 83 and 92 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 83 recites the limitation "the six-minute walk test (6MWT)" in lines 2, 3, and 4. There is insufficient antecedent basis for this limitation in the claim. Claim 83 depends directly from claim 48. Claim 83 is unclear because a 6MWT has not previously been introduced in claim 48. Therefore, it is unclear what test is being referred to. Please correct the limitation to read "a six-minute walk test (6MWT)" in line 2. Likewise, the correction should similarly correct claim 92.
Those claims included in the statement of rejection (Claim 92) but not otherwise discussed are rejected for depending from a rejected claim but failing to remedy the indefiniteness therein.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 48, 49 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and further in view of Sabeti (US 20260071236 A1).
Regarding claim 48, Rodino-Klapac teaches the preamble of the claim, “we report … data from 4 patients with DMD … following a single IV infusion of rAAVrh74.MHCK7.micro dystrophin” (Background and Objective). Rodino-Klapac further describes their “Trial Design” in the Methods section, “Single dose, … rAAVrh74.MHCK7.micro dystrophin was infused over 1- 2 hours via the peripheral limb vein at a dose of 2x1014 vg/kg (10 mL/kg) in the Pediatric Intensive Care Unit at Nationwide Children’s Hospital.” Here, and in combination with the previous citation, Rodino-Klapac teaches the limitation, “… administering to the subject, in a single dose, an effective amount of [a] … composition comprising an adeno-associated virus … particle and a pharmaceutically acceptable carrier.” Given the nature of the study and the location at a hospital, it is certain the composition was provided in a pharmaceutical acceptable carrier.
Rodino-Klapac provide a cartoon map of their rAAVrh74.MHCK7.micro-dystrophin construct (see Figure 1 below).
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Their map highlights the 5’ to 3’ orientation of the teachings of the instant claim: an adeno-associated virus … particle and a pharmaceutically acceptable carrier, wherein the AAV particle comprises an AAV capsid encapsidating a vector genome, wherein the vector genome comprises from 5′ to 3′: a 5′ inverted terminal repeat (ITR); a MHCK7 promoter; an SV40 intron; a micro-dystrophin (μDys) transgene; a … poly (A) tail; and a 3′ ITR.
Rodino-Klapac does not teach the particle is AAV9, nor do they teach the polyadenylation signal is SV40, nor do they teach intrathecal administration.
However, Sabeti also provides a vector map in Figure 9 (see below) showing the 5’ to 3’ orientation and further teaches AAV9 vectors with SV40 poly A tails “AAV viral particles are engineered… AAV9” [0068] and “The polyadenylation signal can be an SV40 polyadenylation signal” [0245].
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Furthermore, Sabeti teaches intrathecal administration “the pharmaceutical formulations described herein may be in a dosage form… adapted for administration … Appropriate routes include… intrathecal…” [0546].
Furthermore, Sabeti provides instructions for using an AAV9 vector that is consistent with both DMD treatment of the instant invention (via intrathecal administration) and Rodino-Klapac, “… while the different serotypes can provide some level of cell, tissue, and/or organ specificity, each serotype still is multi-tropic… tropism of the AAV serotype can be modified by an engineered AAV capsid described herein… variants of wild-type AAV of any serotype can be generated via a method described herein and determined to have a particular cell-specific tropism… including an engineered … variant of wild-type AAV-9 as described herein, the bias for e.g. brain can be reduced or eliminated and/or the muscle septicity increased such that the brain specificity appears reduced in comparison, thus enhancing the specificity for the muscle as compared to the wild-type AAV-9.” [0313].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted the AAV, poly A tail, and administration method of Rodino-Klapac with the AAV9, SV40 polyA tail, and intrathecal administration taught by Sabeti because it amounts to simple substitution of one known element for another to obtain predictable results. A PHOSITA in the field of DMD treatment via adeno-associated virus vector design and gene therapy would necessarily look to alternative AAVs, and regulatory compositions, and methods of administration in order to optimize treatment; particularly those in the field of microdystrophin gene manipulation. Therefore, a PHOSITA would recognize Sabeti’s instructions for manipulating AAV vectors by tuning their tropism toward muscle tissue for DMD treatment. In this particular example highlighted by Sabeti, tuning an AAV9 vector toward muscle tropism. Thus, the PHOSITA would be aware of the tailored AAV9 modifications and successful methods and vectors of Rodino-Klapac and Sabeti. Furthermore, the individual components of the systems of Rodino-Klapac and Sabeti were known in the art and it was known they function the same individually as when combined within said systems. Therefore, a PHOSITA would have predicted the substituted SV40 poly A tail, and muscle tuned AAV9 vector components and intrathecal injection of Rodino-Klapac with the components and intravenous injection of Sabeti.
Regarding claims 49, Rodino-Klapac and Sabeti teach claim 48. Rodino-Klapac further teaches “Male patients with DMD (aged 4- 7 years)” (Methods, Trial Design). Rodino-Klapac’s age range of “4- 7 years” falls entirely within the instant claimed range of “about 6 months to about 7 years old” and therefore, Rodino-Klapac anticipates the claim.
Regarding claims 50, Rodino-Klapac and Sabeti teach claim 48. Recall, Rodino-Klapac teaches “Male patients with DMD (aged 4- 7 years)”(Methods, Trial Design). Rodino-Klapac’s, “4 years” endpoint of their range “4- 7 years” overlaps the “about 4 years” endpoint range of “about 2 years old to about 4 years old” of the instant claim. This examiner is guided by MPEP 2144.05, “The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range.” This examiner has not found any support in the specification to indicate the instant claimed range is critical. Therefore, Rodino-Klapac’s “4- 7 years” range renders the instant claimed range obvious.
Claim(s) 62 and 170 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Chen (Chen et al. Mol Ther. 2021 Mar 3;29(3):989-1000.).
Regarding claim 62, Rodino-Klapac and Sabeti teach claim 48.
Rodino-Klapac and Sabeti do not teach “wherein the effective amount of the intrathecal composition provides a greater therapeutic response than the identical vector genome dose of the AAV9 particle when administered intravenously.”
Chen teaches intrathecal (IT) method has a greater therapeutic response than intravenous (IV) metho and follows with the suggestion to use the IT method in other gene therapies, “Thus, our studies set a therapeutic target dose of either 1 X 1011 vg administered i.t. or 1 X 1012 vg (approximately 4 X 1013 vg/kg) administered i.v. Considering that a 10-fold lower dose can be administered i.t. versus i.v. with similar therapeutic effect, our conclusion would be to favor the i.t. route…” (page 997, 1st column, 2nd paragraph). Chen reinforces their suggestion later “…we conclude that an i.t. approach should be favored” (page 997, 2nd column, 1st paragraph).
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have used the method of DMD treatment of Rodino-Klapac and Sabeti’s, wherein the effective amount of the intrathecal composition provides a greater therapeutic response than the identical vector genome dose of the AAV9 particle when administered intravenously as taught by Chen because Chen provided motivation to use their IT strategy rather than IV. Chen explained the better therapeutic effect and subsequently explicitly suggested using IT methods over IV methods for AAV transgene manipulation therapies. Therefore, a PHOSITA in the field of AAV gene therapy would have reasonably expected to achieve better results with IT methods over IV methods as taught by Chen when using the DMD treatment of Rodino-Klapac-Sabeti.
Regarding claim 170, Chen’s respective therapeutic IT and IV doses of “1 X 1011 vg administered i.t.” or “1 X 1012 vg administered i.v.” equals 90% less IT dose than IV dose. Therefore, Chen’s therapeutic IT: IV dose range is equal to the claimed range “IT composition comprises about 90% or less, … vector genomes than the effective amount IV composition” and therefore overlaps the claimed range, and therefore makes the claimed range obvious.
Regarding claim 171, Chen’s respective therapeutic IT and IV doses of “1 X 1011 vg administered i.t.” or “1 X 1012 vg administered i.v.” equals about 10 times less IT dose than IV dose. Therefore, Chen’s therapeutic IT: IV dose range is equal to the claimed range “AAV9 particle comprises about 10 to 40 times less IV composition” and therefore overlaps the claimed range, and therefore makes the claimed range obvious.
Regarding claims 70 and 71, Rodino-Klapac and Sabeti teach claim 48. Rodino-Klapac further teaches “All 4 patients demonstrated a clinically meaningful improvement on NSAA as early as Day 90, with a mean change from baseline to Year 2 of +7.0.” (Results, Efficacy Outcomes). Furthermore, Table 2 shows an NSAA score increase from about 18- 23. This range overlaps with the two instant claimed ranges, “from about 5 to about 25” and “from about 5 to about 20.” Therefore, the overlapping range of Rodino-Klapac with claim 71’s two instant claimed ranges, “from about 5 to about 25” and “from about 5 to about 20” renders the ranges obvious.
Claim(s) 83 and 92 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Xiao (US 20170368198 A1).
Regarding claim 83, Rodino-Klapac and Sabeti teach claim 48.
Rodino-Klapac and Sabeti do not teach “wherein treating comprises increasing the number of meters walked by the subject in the six-minute walk test (6MWT) subsequent to treatment, compared to a baseline number of meters walked by the subject in the 6MWT, wherein the baseline number of meters walked by the subject in the 6MWT is measured prior to the subject undergoing the treatment.”
Furthermore, Xiao teaches they are in the same field of endeavor “This invention relates to polynucleotides encoding mini-dystrophin proteins, viral vectors comprising the same, and methods of using the same for delivery of mini-dystrophin to a cell or a subject” [Abstract].
Xiao teaches the initial limitation, “wherein treating comprises increasing the number of meters walked by the subject in the six-minute walk test (6MWT) sub sequent to treatment,” by stating the following, “According to some embodiments of the methods of treatment of the disclosure, therapeutic efficacy is determined statistically by comparing the treatment effect of AAV vectors of the disclosures on the average 6MWT performance of treated subjects, such as those with DMD, in comparison with the average 6MWT performance of untreated control subjects with the same type of dystrophinopathy, such as DMD.” In the next sentence, Xiao explains the subject may be included in the control group and therefore also teaches the limitation, “wherein the baseline number of meters walked by the subject in the 6MWT is measured prior to the subject undergoing the treatment.” Xiao explains, “Such controls can have been included in the same studies ...” In the next sentence, Xiao explains the subject’s performance is measured against a baseline, and therefore teaches the limitation, “compared to a baseline number of meters walked by the subject in the 6MWT”. Xiao explains, “Controls can be age matched (or stratified, for example and without limitation, … matched for baseline performance in the 6MWT before any treatment” [0360].
Furthermore, Xiao teaches, “In some of these embodiments, the AAV vector comprises the AAV9 capsid and a genome including a human codon-optimized gene encoding a mini-dystrophin protein” [0361].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have used Xiao’s method of increasing the number of meters walked by the subject in the six-minute walk test with Rodino-Klapac-Sabeti’s method to treat DMD because it is simply combining prior art elements according to known methods to yield predictable results.
Rodino-Klapac and Sabeti method of DMD treatment was obviously known as described above. Similarly, Xiao’s method of increasing the number of meters walked by the subject in the six-minute walk test after DMD transgene treatment was known. In fact, Xiao teaches the 6MWT is the clinical standard “The 6MWT has been established as a reproducible and valid measure of muscle function and mobility of human subjects with muscular dystrophy, in particular, DMD.” [0359]. Therefore, a PHOSITA would necessarily look for improvement in the 6MWT. Therefore, a PHOSITA would have predicted Xiao’s method of increasing the number of meters walked by the subject in the six-minute walk test with Rodino-Klapac-Sabeti’s method to treat DMD.
Regarding claim 92, Rodino-Klapac and Sabeti teach claim 48.
Rodino-Klapac and Sabeti do not teach “wherein increasing the number of meters walked by the subject in the 6MWT comprises increasing by from about 5 meters to about 50 meters, about 5 meters to about 45 meters, about 5 meters to about 40 meters, about 5 meters to about 35 meters, about 5 meters to about 30 meters, about 5 meters to about 25 meters, about 5 meters to about 20 meters, about 5 to about 15 meters or about 5 meters to about 10 meters.”
However, Xiao further teaches 6MWT baselines, “for example and without limitation, into those subjects whose baseline performance is below and above some threshold, such as 200 m, 250 m, 300 m, 350 m, 400 m, 450 m, or 500 m), or some other attribute determined to be clinically relevant.” [0360]. Xiao’s citation, “below and above some threshold, such as 200 m” describes the instant claimed distances of 50 meters, 45, meters, etcetera. Furthermore, Xiao describes the subject’s increased distance with the following statement, “According to certain embodiments of the methods of treatment of the disclosure, a therapeutically effective dose or amount of an AAV vector of the disclosure is effective to increase the average 6MWD of subjects with dystrophinopathy, such as DMD, by about or at least 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, or 100 meters or more compared to similar matched or stratified controls” [0361]. The two statements combined, present ranges that overlap the claimed limitation ranges, for example, “increasing by from about 5 meters to about 50 meters.” Therefore, the claimed ranges are obvious over Xiao’s ranges.
Regarding claim 94, Rodino-Klapac and Sabeti teach claim 48. Rodino-Klapac further envisions “greater μDys transgene expression in skeletal and cardiac muscle” as exemplified by their teaching, “Systemic adeno associated virus (AAV) based gene therapy for DMD faces challenges that require careful rational design of the construct, given the need to target cardiac muscle and broadly distributed skeletal muscle tissue, and the package limitation of AAV.” (Background and Objective). Furthermore, Rodino-Klapac teach their [Symbol font/0x6D]Dys expression was greater in skeletal and cardiac muscle versus the liver in their Results and Safety section by stating the expression was localized, “Systemic gene transfer resulted in robust levels of micro dystrophin protein expression localized to the sarcolemma as shown by immunofluorescence and western blot.”
Claim(s) 172 and 173 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Choi (US 20140017201 A1).
Regarding claim 172, Rodino-Klapac and Sabeti teach claim 48.
Choi teaches their SEQ ID NO 16. Choi’s SEQ ID NO 16 is 130 nucleotides (same length as instant SEQ ID No 1) and matches instant SEQ ID NO 1 100% as shown below (Choi_NCBI Blast_792_SEQIDNO_1_2026 Oct 4. https://blast.ncbi.nlm.nih.gov/Blast.cgi).
SEQ ID NO 1 1 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTT 60
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SEQ ID NO 16 1 CTGCGCGCTCGCTCGCTCACTGAGGCCGCCCGGGCAAAGCCCGGGCGTCGGGCGACCTTT 60
SEQ ID NO 1 61 GGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACT 120
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SEQ ID NO 16 61 GGTCGCCCGGCCTCAGTGAGCGAGCGAGCGCGCAGAGAGGGAGTGGCCAACTCCATCACT 120
SEQ ID NO 1 121 AGGGGTTCCT 130
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SEQ ID NO 16 121 AGGGGTTCCT 130
Choi describes their SEQ ID NO 16, “It is contemplated that the ITRs of AAV serotype 2 may be used (e.g.: SEQ ID NO: … 16 …” [0077]. Choi further suggest a motivation for utilizing this particular ITR or other compatible ITR’s “However, ITRs from other suitable serotypes may be selected from among any AAV serotype known in the art” [0077]. Choi goes even further providing motivation to use their SEQ ID NO 16 by preaching the benefits of its tolerance for mutations while maintaining functionality, “As described previously …, mutations within the terminal repeat sequences of AAV plasmids are well tolerated in generating functional AAV vectors… Therefore, … it is expected that any 5' ITR sequence that carries the terminal resolution site (i.e.: SEQ. ID. NOS. … 16 …) would produce vectors with the same functionality” [0112]. Furthermore, Choi shows they are in the same field of endeavor, delivering transgenes with vectors, “The present invention relates to viral vectors that are capable of delivering a heterologous gene...” [Abstract].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 1 in favor of Choi’s SEQ ID NO 16 in order to arrive at the claimed method of treating DMD with the claimed 5' ITR sequence because Choi provided motivation to use their 5’ ITR by explaining the mutation tolerance benefits of their 5’ ITR. Furthermore, the 5’ ITR sequence of Choi is the same sequence as Rodino-Klapac-Sabeti’s, therefore, a PHOSITA would reasonably expect the substitution to be successful.
Regarding claim 173, Rodino-Klapac and Sabeti teach claim 48.
Choi teaches their SEQ ID NO 9. Choi’s SEQ ID NO 9 is 130 nucleotides (same length as instant SEQ ID No 7) and matches instant SEQ ID NO 7 100% as shown below (Choi_NCBI Blast_792_SEQIDNO_7_2026 Oct 4. https://blast.ncbi.nlm.nih.gov/Blast.cgi).
SEQ ID No 7 1 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGG 60
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SEQ ID NO 9 1 AGGAACCCCTAGTGATGGAGTTGGCCACTCCCTCTCTGCGCGCTCGCTCGCTCACTGAGG 60
SEQ ID No 7 61 CCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 120
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SEQ ID NO 9 61 CCGGGCGACCAAAGGTCGCCCGACGCCCGGGCTTTGCCCGGGCGGCCTCAGTGAGCGAGC 120
SEQ ID No 7 121 GAGCGCGCAG 130
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SEQ ID NO 9 121 GAGCGCGCAG 130
Choi describes their SEQ ID NO 9, “The invention also relates, in part, to viral vectors carrying a self-complementary genome. The self-complementary vector genome can include, … and a 3' ITR … wherein the genome comprises, nucleic acid sequences … of: SEQ ID NOs: … 9” [0011]. Choi further suggest a motivation for utilizing this particular ITR or other compatible ITR’s “However, ITRs from other suitable serotypes may be selected from among any AAV serotype known in the art” [0077]. Choi goes even further providing motivation to use their SEQ ID NO 16 by preaching the benefits of its tolerance for mutations while maintaining functionality, “As described previously …, mutations within the terminal repeat sequences of AAV plasmids are well tolerated in generating functional AAV vectors… Therefore, … it is expected that any 5' ITR sequence that carries the terminal resolution site (i.e.: SEQ. ID. NOS. … 16 …) would produce vectors with the same functionality” [0112]. Furthermore, Choi shows they are in the same field of endeavor, delivering transgenes with vectors, “The present invention relates to viral vectors that are capable of delivering a heterologous gene...” [Abstract].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 7 in favor of Choi’s SEQ ID NO 9 in order to arrive at the claimed method of treating DMD with the claimed 3’ ITR because it is a simple substitution of one known element for another to obtain predictable results. Rodino-Klapac-Sabeti and Choi both envisioned and successfully utilized the 3’ ITR in vector-mediated transgene manipulation. Therefore, a PHOSITA would have predicted the substitution of Choi’s identical 3’ ITR would function identically to Rodino-Klapac-Sabeti’s 3’ ITR and therefore function similarly successfully.
Claim(s) 174 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Pule (US 20200308600 A1).
Regarding claim 174, Rodino-Klapac and Sabeti teach claim 48.
Pule teaches their SEQ ID NO 33. Pule’s SEQ ID NO 33 is 771 nucleotides (same length as instant SEQ ID No 2) and matches instant SEQ ID NO 2 100% as shown in Index A below (Pule_NCBI Blast_792_SEQIDNO2_2026 Oct 5. https://blast.ncbi.nlm.nih.gov/Blast.cgi). Pule describes their SEQ ID NO 33, “The nucleic acid sequences of murine muscle creatine kinase and a-myosin heavy chain (MHCK7) promoter are available from GenBank (Accession numbers AF188002.1 and U71441.1 respectively). The combined sequence is shown below as SEQ ID No. 33…” [0161]. Furthermore, Pule shows they are in the same field of endeavor, delivering transgenes with vectors, “The present invention provides a kit of vectors for transducing an immune cell with multiple transgenes comprising:… (ii) a second vector which comprises a second transgene wherein expression of the second transgene within a host cell is dependent upon expression of the transcription factor.” [Abstract]. Furthermore, Pule teaches their embodiments are tissue specific, particularly muscle tissue specific, “The transcription factor [and therefore the transgene] may be a tissue-specific transcription factor that is not expressed in an immune cell and could be used to drive transcription [of the transgene] from its cognate tissue-specific promoter. Examples of tissue-specific transcription factors include those from muscle cells” [0060].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 2 in favor of Pule’s SEQ ID NO 33 in order to arrive at the claimed method of treating DMD with the claimed MHCK7 promoter because it is a simple substitution of one known element for another to obtain predictable result. Rodino-Klapac-Sabeti’s and Pule were aware of the MHCK7 promoter and both successfully used the MHCK7 promoter in their muscle tissue specific transgene manipulations. Furthermore, because Rodino-Klapac-Sabeti and Pule both envisioned and utilized the MHCK7 promoter in a muscle tissue specific manner, a PHOSITA would have predicted the substitution of Pule’s identical MHCK7 promoter would function identically to Rodino-Klapac-Sabeti’s MHCK7 promoter.
Claim(s) 175 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Meyer (US 20240189452 A1).
Regarding claim 174, Rodino-Klapac and Sabeti teach claim 48.
Meyer teaches their SEQ ID NO 7. Meyer’s SEQ ID NO 7 is 101 nucleotides and its bases 2- 99 match instant SEQ ID NO 4 100% as shown below (Meyer_NCBI Blast_792_SEQIDNO4_2026 Oct 5. https://blast.ncbi.nlm.nih.gov/Blast.cgi).
SEQ ID NO 7 1 G GTAAGTTTAGTCTTTTTTGTCTTTTATTTCAGGTCCCGGATCCGGTGGTGGTGCAAATCA 61
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SEQ ID NO 4 1 GTAAGTTTAGTCTTTTTTGTCTTTTATTTCAGGTCCCGGATCCGGTGGTGGTGCAAATCA 60
SEQ ID NO 7 62 AAGAACTGCTCCTCAGTCGATGTTGCCTTTACTTCTAG GC 101
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SEQ ID NO 4 61 AAGAACTGCTCCTCAGTCGATGTTGCCTTTACTTCTAG 98
Meyer describes their SEQ ID NO 7 in their Table 4. Table 4 states in the header “Molecular Features of plasmid scAAV9…,” and further describes the inclusion, “SV40 intronic sequence.” Meyer shows they are in the same field of endeavor, delivering transgenes with vectors, “Methods and materials for treating Pitt Hopkins Syndrome comprising intrathecal delivery of recombinant Adeno-associated virus 9 (rAAV9) encoding Methyl-CpG binding protein 2 (MECP2) are provided.” [Abstract].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 4 in favor of Meyer’s SEQ ID NO 7 in order to arrive at the claimed method of treating DMD with the claimed SV40 intron because it is a simple substitution of one known element for another to obtain predictable result. Rodino-Klapac-Sabeti and Meyer both envisioned and successfully utilized the SV40 intron in vector-mediated transgene manipulation. Therefore, a PHOSITA would have predicted the substitution of Choi’s identical SV40 intron would function identically to Rodino-Klapac-Sabeti’s SV40 intron function similarly successfully.
Claim(s) 176 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Rao (US 20260000788 A1).
Regarding claim 176, Rodino-Klapac and Sabeti teach claim 48.
Rao teaches their SEQ ID NO 5. Rao’s SEQ ID NO 5 is 7541 nucleotides and its bases 961- 4548 match instant SEQ ID NO 5 100% as shown in Index A below (Rao_NCBI Blast 792SEQIDNO5 query. 2026 Oct 4. https://blast.ncbi.nlm.nih.gov/Blast.cgi). Rao describes their SEQ ID NO 5 where they describe the construction of the vector, “The vector comprises AAV9 ... micro-dystrophin vector is constructed by the steps of: constructed the plasmid vector by sub-cloning the ΔR4-23/AC micro-dystrophin gene (μDys) … to the recipient plasmid pssAAV-CAG-eGFP, … such that the micro-dystrophin gene is placed downstream to the CAG-Kozak sequence in the final construct designated as pssAAV-CAG-Kozak-micro-dystrophin (CAG-Kozak-μDys) comprising sequence Id 5, to ensure the ubiquitous and greater translational efficacy of dystrophin” [0017- 0019]. Rao reinforces they are in the same field of endeavor, delivering transgenes with vectors to treat DMD, “the present invention relates to bioengineered AAV9 vector carrying optimized (sic) transgene for Duchenne muscular dystrophy gene therapy” [Abstract].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 5 in favor of Rao’s SEQ ID NO 5 in order to arrive at the claimed method of treating DMD with the claimed micro-dystrophin transgene of instant SEQ ID NO:5 because it is a simple substitution of one known element for another to obtain predictable results. A PHOSITA in the field of [Symbol font/0x6D]Dys treatment via transgene insertion would be aware of, and recognize the similar vectors of Rodino-Klapac-Sabeti and Rao. In particular, a PHOSITA would recognize and distinguish the [Symbol font/0x6D]Dys gene component of Rodino-Klapac-Sabeti’s SEQ ID NO 5 within Rao’s SEQ ID NO 5. Furthermore, because Rodino-Klapac-Sabeti and Rao both envisioned and utilized the [Symbol font/0x6D]Dys gene in vector-mediated transgene manipulation, a PHOSITA would have predicted the substitution of Rao’s [Symbol font/0x6D]Dys gene within their SEQ ID NO 5 would function identically to Rodino-Klapac-Sabeti’s [Symbol font/0x6D]Dys gene of instant SEQ ID NO 5.
Claim(s) 177 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rodino-Klapac (Rodino-Klapac et al. 25th International Annual Congress of the World Muscle Society. 30 Sep 2020), and Sabeti (US 20260071236 A1) as applied to claim 48 above, and further in view of Mohr (US 20240033377 A1, effectively filed 2020 Dec. 9).
Regarding claim 177, Rodino-Klapac and Sabeti teach claim 48.
Mohr teaches their SEQ ID NO 40427. Mohr’s SEQ ID NO 40427 is 82 nucleotides (same length as instant SEQ ID No 6) and matches instant SEQ ID NO 6 100% as shown below (Mohr_NCBI Blast_792_SEQIDNO_6_2026 oct 4. https://blast.ncbi.nlm.nih.gov/Blast.cgi).
SEQ ID No 6 1 AACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
SEQ ID NO 40427 1 AACTTGTTTATTGCAGCTTATAATGGTTACAAATAAAGCAATAGCATCACAAATTTCACA 60
SEQ ID No 6 61 AATAAAGCAtttttttCACTGC 82
||||||||||||||||||||||
SEQ ID NO 40427 61 AATAAAGCATTTTTTTCACTGC 82
Mohr describes their SEQ ID NO 40427 in their Table 10. Table 10 states in the header “Poly (A) sequences,” and further describes the inclusion, “SEQ ID NO 40427” with the added Poly (A) column descriptor “SV40 short.” Further description is provided in Table 26, with the descriptor “PolyA signal.” Mohr shows they are in the same field of endeavor, delivering transgenes with vectors, “Provided herein polynucleotides configured for incorporation into recombinant adeno-associated virus (AAV) vectors” [Abstract].
It would have been obvious for a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to have substituted Rodino-Klapac and Sabeti’s SEQ ID NO 6 in favor of Mohr’s SEQ ID NO 40427 in order to arrive at the claimed method of treating DMD with the claimed SV40 poly (A) tail because it is a simple substitution of one known element for another to obtain predictable result. Rodino-Klapac-Sabeti and Mohr both envisioned and successfully utilized the SV40 poly (A) tail in vector-mediated transgene manipulation. Therefore, a PHOSITA would have predicted the substitution of Mohr’s identical SV40 poly (A) tail would function identically to Rodino-Klapac-Sabeti’s SV40 poly (A) tail and function similarly successfully.
Index A
Sequence alignment of Pule’s SEQ ID NO 33 (Subject) and instant application’s SEQ ID NO 2 (Query):
Query 1 CCTTCAGATTAAAAATAACTGAGGTAAGGGCCTGGGTAGGGGAGGTGGTGTGAGACGCTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1 CCTTCAGATTAAAAATAACTGAGGTAAGGGCCTGGGTAGGGGAGGTGGTGTGAGACGCTC 60
Query 61 CTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTaa 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 61 CTGTCTCTCCTCTATCTGCCCATCGGCCCTTTGGGGAGGAGGAATGTGCCCAAGGACTAA 120
Query 121 aaaaaGGCCATGGAGCCAGAGGGGCGAGGGCAACAGACCTTTCATGGGCAAACCTTGGGG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 121 AAAAAGGCCATGGAGCCAGAGGGGCGAGGGCAACAGACCTTTCATGGGCAAACCTTGGGG 180
Query 181 CCCTGCTGTCTAGCATGCCCCACTACGGGTCTAGGCTGCCCATGTAAGGAGGCAAGGCCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 181 CCCTGCTGTCTAGCATGCCCCACTACGGGTCTAGGCTGCCCATGTAAGGAGGCAAGGCCT 240
Query 241 GGGGACACCCGAGATGCCTGGTTATAATTAACCCAGACATGTGGCTGccccccccccccc 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 241 GGGGACACCCGAGATGCCTGGTTATAATTAACCCAGACATGTGGCTGCCCCCCCCCCCCC 300
Query 301 AACACCTGCTGCCTCTAAAAATAACCCTGTCCCTGGTGGATCCCCTGCATGCGAAGATCT 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 301 AACACCTGCTGCCTCTAAAAATAACCCTGTCCCTGGTGGATCCCCTGCATGCGAAGATCT 360
Query 361 TCGAACAAGGCTGTGGGGGACTGAGGGCAGGCTGTAACAGGCTTGGGGGCCAGGGCTTAT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 361 TCGAACAAGGCTGTGGGGGACTGAGGGCAGGCTGTAACAGGCTTGGGGGCCAGGGCTTAT 420
Query 421 ACGTGCCTGGGACTCCCAAAGTATTACTGTTCCATGTTCCCGGCGAAGGGCCAGCTGTCC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 421 ACGTGCCTGGGACTCCCAAAGTATTACTGTTCCATGTTCCCGGCGAAGGGCCAGCTGTCC 480
Query 481 CCCGCCAGCTAGACTCAGCACTTAGTTTAGGAACCAGTGAGCAAGTCAGCCCTTGGGGCA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 481 CCCGCCAGCTAGACTCAGCACTTAGTTTAGGAACCAGTGAGCAAGTCAGCCCTTGGGGCA 540
Query 541 GCCCATACAAGGCCATGGGGCTGGGCAAGCTGCACGCCTGGGTCCGGGGTGGGCACGGTG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 541 GCCCATACAAGGCCATGGGGCTGGGCAAGCTGCACGCCTGGGTCCGGGGTGGGCACGGTG 600
Query 601 CCCGGGCAACGAGCTGAAAGCTCATCTGCTCTCAGGGGCCCCTCCCTGGGGACAGCCCCT 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 601 CCCGGGCAACGAGCTGAAAGCTCATCTGCTCTCAGGGGCCCCTCCCTGGGGACAGCCCCT 660
Query 661 CCTGGCTAGTCACACCCTGTAGGCTCCTCTATATAACCCAGGGGCACAGGGGCTGCCCTC 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 661 CCTGGCTAGTCACACCCTGTAGGCTCCTCTATATAACCCAGGGGCACAGGGGCTGCCCTC 720
Query 721 ATTCTACCACCACCTCCACAGCACAGACAGACACTCAGGAGCCAGCCAGCC 771
|||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 721 ATTCTACCACCACCTCCACAGCACAGACAGACACTCAGGAGCCAGCCAGCC 771
Sequence alignment of Rao’s SEQ ID NO 5 (Subject) and instant application’s SEQ ID NO 5 (Query):
Query 1 ATGCTTTGGTGGGAAGAAGTAGAGGACTGTTATGAAAGAGAAGATGTTCAAAAGAAAACA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 961 ATGCTTTGGTGGGAAGAAGTAGAGGACTGTTATGAAAGAGAAGATGTTCAAAAGAAAACA 1020
Query 61 TTCACAAAATGGGTAAATGCACAATTTTCTAAGTTTGGGAAGCAGCATATTGAGAACCTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1021 TTCACAAAATGGGTAAATGCACAATTTTCTAAGTTTGGGAAGCAGCATATTGAGAACCTC 1080
Query 121 TTCAGTGACCTACAGGATGGGAGGCGCCTCCTAGACCTCCTCGAAGGCCTGACAGGGCAA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1081 TTCAGTGACCTACAGGATGGGAGGCGCCTCCTAGACCTCCTCGAAGGCCTGACAGGGCAA 1140
Query 181 AAACTGCCAAAAGAAAAAGGATCCACAAGAGTTCATGCCCTGAACAATGTCAACAAGGCA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1141 AAACTGCCAAAAGAAAAAGGATCCACAAGAGTTCATGCCCTGAACAATGTCAACAAGGCA 1200
Query 241 CTGCGGGTTTTGCAGAACAATAATGTTGATTTAGTGAATATTGGAAGTACTGACATCGTA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1201 CTGCGGGTTTTGCAGAACAATAATGTTGATTTAGTGAATATTGGAAGTACTGACATCGTA 1260
Query 301 GATGGAAATCATAAACTGACTCTTGGTTTGATTTGGAATATAATCCTCCACTGGCAGGTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1261 GATGGAAATCATAAACTGACTCTTGGTTTGATTTGGAATATAATCCTCCACTGGCAGGTC 1320
Query 361 AAAAATGTAATGAAAAATATCATGGCTGGATTGCAACAAACCAACAGTGAAAAGATTCTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1321 AAAAATGTAATGAAAAATATCATGGCTGGATTGCAACAAACCAACAGTGAAAAGATTCTC 1380
Query 421 CTGAGCTGGGTCCGACAATCAACTCGTAATTATCCACAGGTTAATGTAATCAACTTCACC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1381 CTGAGCTGGGTCCGACAATCAACTCGTAATTATCCACAGGTTAATGTAATCAACTTCACC 1440
Query 481 ACCAGCTGGTCTGATGGCCTGGCTTTGAATGCTCTCATCCATAGTCATAGGCCAGACCTA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1441 ACCAGCTGGTCTGATGGCCTGGCTTTGAATGCTCTCATCCATAGTCATAGGCCAGACCTA 1500
Query 541 TTTGACTGGAATAGTGTGGTTTGCCAGCAGTCAGCCACACAACGACTGGAACATGCATTC 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1501 TTTGACTGGAATAGTGTGGTTTGCCAGCAGTCAGCCACACAACGACTGGAACATGCATTC 1560
Query 601 AACATCGCCAGATATCAATTAGGCATAGAGAAACTACTCGATCCTGAAGATGTTGATACC 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1561 AACATCGCCAGATATCAATTAGGCATAGAGAAACTACTCGATCCTGAAGATGTTGATACC 1620
Query 661 ACCTATCCAGATAAGAAGTCCATCTTAATGTACATCACATCACTCTTCCAAGTTTTGCCT 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1621 ACCTATCCAGATAAGAAGTCCATCTTAATGTACATCACATCACTCTTCCAAGTTTTGCCT 1680
Query 721 CAACAAGTGAGCATTGAAGCCATCCAGGAAGTGGAAATGTTGCCAAGGCCACCTAAAGTG 780
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1681 CAACAAGTGAGCATTGAAGCCATCCAGGAAGTGGAAATGTTGCCAAGGCCACCTAAAGTG 1740
Query 781 ACTAAAGAAGAACATTTTCAGTTACATCATCAAATGCACTATTCTCAACAGATCACGGTC 840
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1741 ACTAAAGAAGAACATTTTCAGTTACATCATCAAATGCACTATTCTCAACAGATCACGGTC 1800
Query 841 AGTCTAGCACAGGGATATGAGAGAACTTCTTCCCCTAAGCCTCGATTCAAGAGCTATGCC 900
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1801 AGTCTAGCACAGGGATATGAGAGAACTTCTTCCCCTAAGCCTCGATTCAAGAGCTATGCC 1860
Query 901 TACACACAGGCTGCTTATGTCACCACCTCTGACCCTACACGGAGCCCATTTCCTTCACAG 960
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1861 TACACACAGGCTGCTTATGTCACCACCTCTGACCCTACACGGAGCCCATTTCCTTCACAG 1920
Query 961 CATTTGGAAGCTCCTGAAGACAAGTCATTTGGCAGTTCATTGATGGAGAGTGAAGTAAAC 1020
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1921 CATTTGGAAGCTCCTGAAGACAAGTCATTTGGCAGTTCATTGATGGAGAGTGAAGTAAAC 1980
Query 1021 CTGGACCGTTATCAAACAGCTTTAGAAGAAGTATTATCGTGGCTTCTTTCTGCTGAGGAC 1080
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 1981 CTGGACCGTTATCAAACAGCTTTAGAAGAAGTATTATCGTGGCTTCTTTCTGCTGAGGAC 2040
Query 1081 ACATTGCAAGCACAAGGAGAGATTTCTAATGATGTGGAAGTGGTGAAAGACCAGTTTCAT 1140
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2041 ACATTGCAAGCACAAGGAGAGATTTCTAATGATGTGGAAGTGGTGAAAGACCAGTTTCAT 2100
Query 1141 ACTCATGAGGGGTACATGATGGATTTGACAGCCCATCAGGGCCGGGTTGGTAATATTCTA 1200
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2101 ACTCATGAGGGGTACATGATGGATTTGACAGCCCATCAGGGCCGGGTTGGTAATATTCTA 2160
Query 1201 CAATTGGGAAGTAAGCTGATTGGAACAGGAAAATTATCAGAAGATGAAGAAACTGAAGTA 1260
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2161 CAATTGGGAAGTAAGCTGATTGGAACAGGAAAATTATCAGAAGATGAAGAAACTGAAGTA 2220
Query 1261 CAAGAGCAGATGAATCTCCTAAATTCAAGATGGGAATGCCTCAGGGTAGCTAGCATGGAA 1320
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2221 CAAGAGCAGATGAATCTCCTAAATTCAAGATGGGAATGCCTCAGGGTAGCTAGCATGGAA 2280
Query 1321 AAACAAAGCAATTTACATAGAGTTTTAATGGATCTCCAGAATCAGAAACTGAAAGAGTTG 1380
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2281 AAACAAAGCAATTTACATAGAGTTTTAATGGATCTCCAGAATCAGAAACTGAAAGAGTTG 2340
Query 1381 AATGACTGGCTAACAAAAACAGAAGAAAGAACAAGGAAAATGGAGGAAGAGCCTCTTGGA 1440
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2341 AATGACTGGCTAACAAAAACAGAAGAAAGAACAAGGAAAATGGAGGAAGAGCCTCTTGGA 2400
Query 1441 CCTGATCTTGAAGACCTAAAACGCCAAGTACAACAACATAAGGTGCTTCAAGAAGATCTA 1500
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2401 CCTGATCTTGAAGACCTAAAACGCCAAGTACAACAACATAAGGTGCTTCAAGAAGATCTA 2460
Query 1501 GAACAAGAACAAGTCAGGGTCAATTCTCTCACTCACATGGTGGTGGTAGTTGATGAATCT 1560
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2461 GAACAAGAACAAGTCAGGGTCAATTCTCTCACTCACATGGTGGTGGTAGTTGATGAATCT 2520
Query 1561 AGTGGAGATCACGCAACTGCTGCTTTGGAAGAACAACTTAAGGTATTGGGAGATCGATGG 1620
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2521 AGTGGAGATCACGCAACTGCTGCTTTGGAAGAACAACTTAAGGTATTGGGAGATCGATGG 2580
Query 1621 GCAAACATCTGTAGATGGACAGAAGACCGCTGGGTTCTTTTACAAGACATCCTTCTCAAA 1680
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2581 GCAAACATCTGTAGATGGACAGAAGACCGCTGGGTTCTTTTACAAGACATCCTTCTCAAA 2640
Query 1681 TGGCAACGTCTTACTGAAGAACAGTGCCTTTTTAGTGCATGGCTTTCAGAAAAAGAAGAT 1740
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2641 TGGCAACGTCTTACTGAAGAACAGTGCCTTTTTAGTGCATGGCTTTCAGAAAAAGAAGAT 2700
Query 1741 GCAGTGAACAAGATTCACACAACTGGCTTTAAAGATCAAAATGAAATGTTATCAAGTCTT 1800
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2701 GCAGTGAACAAGATTCACACAACTGGCTTTAAAGATCAAAATGAAATGTTATCAAGTCTT 2760
Query 1801 CAAAAACTGGCCGTTTTAAAAGCGGATCTAGAAAAGAAAAAGCAATCCATGGGCAAACTG 1860
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2761 CAAAAACTGGCCGTTTTAAAAGCGGATCTAGAAAAGAAAAAGCAATCCATGGGCAAACTG 2820
Query 1861 TATTCACTCAAACAAGATCTTCTTTCAACACTGAAGAATAAGTCAGTGACCCAGAAGACG 1920
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2821 TATTCACTCAAACAAGATCTTCTTTCAACACTGAAGAATAAGTCAGTGACCCAGAAGACG 2880
Query 1921 GAAGCATGGCTGGATAACTTTGCCCGGTGTTGGGATAATTTAGTCCAAAAACTTGAAAAG 1980
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2881 GAAGCATGGCTGGATAACTTTGCCCGGTGTTGGGATAATTTAGTCCAAAAACTTGAAAAG 2940
Query 1981 AGTACAGCACAGATTTCACAGGCTGTCACCACCACTCAGCCATCACTAACACAGACAACT 2040
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 2941 AGTACAGCACAGATTTCACAGGCTGTCACCACCACTCAGCCATCACTAACACAGACAACT 3000
Query 2041 GTAATGGAAACAGTAACTACGGTGACCACAAGGGAACAGATCCTGGTAAAGCATGCTCAA 2100
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3001 GTAATGGAAACAGTAACTACGGTGACCACAAGGGAACAGATCCTGGTAAAGCATGCTCAA 3060
Query 2101 GAGGAACTTCCACCACCACCTCCCCAAAAGAAGAGGCAGATTACTGTGGATCTTGAAAGA 2160
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3061 GAGGAACTTCCACCACCACCTCCCCAAAAGAAGAGGCAGATTACTGTGGATCTTGAAAGA 3120
Query 2161 CTCCAGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTG 2220
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3121 CTCCAGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTG 3180
Query 2221 ATCAAGGGATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTC 2280
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3181 ATCAAGGGATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTC 3240
Query 2281 GAGAAAGTCAAGGCACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTC 2340
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3241 GAGAAAGTCAAGGCACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTC 3300
Query 2341 AATGACCTTGCTCGCCAGCTTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGC 2400
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3301 AATGACCTTGCTCGCCAGCTTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGC 3360
Query 2401 ACTCTGGAAGACCTGAACACCAGATGGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTC 2460
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3361 ACTCTGGAAGACCTGAACACCAGATGGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTC 3420
Query 2461 AGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCCAGCATCTCAGCACTTTCTTTCCACG 2520
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3421 AGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCCAGCATCTCAGCACTTTCTTTCCACG 3480
Query 2521 TCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAAAGTGCCCTACTATATCAAC 2580
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3481 TCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAAAGTGCCCTACTATATCAAC 3540
Query 2581 CACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGCTCTACCAGTCTTTA 2640
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3541 CACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGCTCTACCAGTCTTTA 3600
Query 2641 GCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCCGAAGACTG 2700
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3601 GCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCCGAAGACTG 3660
Query 2701 CAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACCAG 2760
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3661 CAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACCAG 3720
Query 2761 CACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACC 2820
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3721 CACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACC 3780
Query 2821 ACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTG 2880
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3781 ACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTG 3840
Query 2881 GATATGTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGT 2940
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3841 GATATGTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGT 3900
Query 2941 GTCCTGTCTTTTAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTAC 3000
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3901 GTCCTGTCTTTTAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTAC 3960
Query 3001 AGATACCTTTTCAAGCAAGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGC 3060
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 3961 AGATACCTTTTCAAGCAAGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGC 4020
Query 3061 CTCCTTCTGCATGATTCTATCCAAATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGG 3120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4021 CTCCTTCTGCATGATTCTATCCAAATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGG 4080
Query 3121 GGCAGTAACATTGAGCCAAGTGTCCGGAGCTGCTTCCAATTTGCTAATAATAAGCCAGAG 3180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4081 GGCAGTAACATTGAGCCAAGTGTCCGGAGCTGCTTCCAATTTGCTAATAATAAGCCAGAG 4140
Query 3181 ATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAACCCCAGTCCATGGTGTGGCTG 3240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4141 ATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAACCCCAGTCCATGGTGTGGCTG 4200
Query 3241 CCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAGGCCAAATGTAACATC 3300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4201 CCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAGGCCAAATGTAACATC 4260
Query 3301 TGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTTAATTATGAC 3360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4261 TGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTTAATTATGAC 4320
Query 3361 ATCTGCCAAAGCTGCtttttttCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTATCCC 3420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4321 ATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTATCCC 4380
Query 3421 ATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTA 3480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4381 ATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTA 4440
Query 3481 CTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTG 3540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4441 CTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTG 4500
Query 3541 CCAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACTGACACAATT 3588
||||||||||||||||||||||||||||||||||||||||||||||||
Sbjct 4501 CCAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACTGACACAATT 4548
End Index A.
Conclusion
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/AARON DUREL WARD/Examiner, Art Unit 1636
/NEIL P HAMMELL/Supervisory Patent Examiner, Art Unit 1636
