DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/10/2025 has been entered.
Applicant’s arguments filed on July 10, 2025 have been receive and entered. Claims 2-5, 7-10, 12, 14-24 26-30 and33 have been canceled. Claims 1, 6, 11, 13, 25, 31-32, 34-35 and 36 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-13 (group I) in the reply filed on March 4, 2020 was acknowledged. Applicant’s election without traverse of species C1E1, AAVrh10 and constitutively active promoter for species of nucleic acid, vector and promoter respectively is acknowledged. However, upon further consideration, election of species requirements was withdrawn and all the non-elected species of nucleic acid, vectors and promoter were rejoined with the elected species.
Claims 1, 6, 11, 13, 25, 31-32, 34-35 and 36 are under consideration.
Priority
This application is a divisional of US application no 15/167,729 05/27/2016, now US patent no 10214731, which claims priority from US provisional application 62/324,183 filed on 04/18/2016 that claims priority from US provisional application no 62/167,603 filed on 05/28/2015.
Allowable Subject Matter
The following claim 1 is drafted by the examiner and considered to distinguish patentably over the art of record in this application, claim 1 is presented to applicant for consideration:
A composition comprising a therapeutic effective amount of recombinant adeno-associated virus (AAV) vector comprising a cytomegalovirus (CMV) enhancer chicken-3-actin promoter (CAG promoter) operably linked to human C1EI cDNA sequence and the rabbit 3-globin polyadenylation signal, wherein the vector is an AAVrh.10 or AAV9 vector and a pharmaceutically acceptable carrier, wherein said composition is capable of producing human C1EI protein that is capable of treating a deficiency in a functional plasma hC1EI, and wherein hC1E1 expression and/or activity is greater than the clinical threshold value for 6 weeks after the composition is administered to a mammal.
Withdrawn- Claim Rejections - 35 USC § 103
Claims 1, 6, 11, 13, 25, 31-32, 34-25 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Adhi et al (Investigative Ophthalmology & Visual Science, 2012, ARVO annual meeting abstract. 53; 1888), Hu et al (J Gene Med. 2010, 12(9): 766–778) as evidenced by Sodhi et al (Molecular Therapy vol. 15 no. 3, 481–491 2007), Sondhi (Human Gene therapy methods, 2012, 23, 324-335)/ Ballantyne et al (PLoS One, 2015, 1-20) and further in view of Roeth et al (WO/2012/122025, dated 09/13/2012). Upon further consideration, the instant rejection has been withdrawn in view of the new rejection set forth below.
New- Claim Rejections - 35 USC § 103
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.
Claims 1, 6, 13, 25, 32, are rejected under 35 U.S.C. 103 as being unpatentable over Adhi et al (Investigative Ophthalmology & Visual Science, 2012, ARVO annual meeting abstract. 53; 1888, art of record), Hu et al (J Gene Med. 2010, 12(9): 766–778, IDS) and Sondhi (Human Gene therapy methods, 2012, 23, 324-335)/ Ballantyne et al (PLoS One, 2015, 1-20, art of record).
Claims are directed to a recombinant adeno-associated virus (AAV) vector, comprising a chicken beta-actin promoter operably linked to a nucleic acid sequence which encodes human C1 esterase inhibitor (C1EI) and a rabbit beta globin polyadenylation signal, wherein the vector is an AAVrh.10 or AAV9 vector.
Claim interpretation: Instant rejection is applied to address both vector alternatives recited in the claim with intended use of expressing hC1E1 in treating a disorder.
With respect to claim 1, Adhi et al teach an adeno-associated virus serotype 8 (AAV8) vector comprising a nucleic acid encoding human c-esterase inhibitor, wherein intravitreal injection result in sustained expression of hC1E1 (se abstract). The vector disclosed in Adhi is capable of producing hC1E1 because results show significant reduction in the leakage (see abstract) suggesting alleviating the deficiency of C1E1 that causes vascular leakage.
Adhi differs from claimed invention by not disclosing (i) use of chicken beta active promoter operably linked to a nucleic acid sequence which encodes human C1 esterase inhibitor and a rabbit beta globin poly A sequence and (ii) use of another adeno-associated virus such as rh10 or AAV9.
However, use of constitutively active promoter with different AAV serotype to express gene of interest was routine in art before the effective filing date of the instant invention., Hu et al teach comparing recombinant AAV vectors expressing firefly luciferase driven by the cytomegalovirus-enhanced chicken β-actin promoter (AAV.CB.LUC) and a poly A signal that were packaged with viral capsids AAV 8, 9, and rh10 (see page 2, under material and method, para. 3). Regarding claims 13, Hu et al teach a composition comprising the AAV8, 9 and rh10 vector in a pharmaceutical acceptable carrier (phosphate buffered saline) (see 768, col. 1, para. 1). It is disclosed that AAV rh10 injected intravenously (see page 768, col. 1, para. 2) to the subject provided the greatest level of expression followed by AAV9 and AAV8 as compared to all other serotypes (see page 770, last para. page 771, col. 1, past para.).
The combination of references differs from claimed invention by not disclosing use of modular elements (CB promoter and poly A signal comprises a rabbit beta globulin poly A.
Sondhi et al provided the motivation to use AAVrh.10, an AAV isolated from rhesus monkeys, with the added advantage that it is nonhuman in origin, allowing it to bypass the anti-human AAV immunity that is common in the population (se page 325). Sondhi teaches AAVrh10 comprising an expression cassette consist of chicken beta actin promoter, gene of interest and a rabbit beta globin polyA (see page 325, col. 1, para. 3) has a good safety profile. Likewise, Ballantyne teach generating AAVrh10 comprising chicken beta actin promoter operably linked to a coding sequence of gene of interest and rabbit-beta globin poly A to express higher level of gene of interest as compared to AAV8 (see page 5, para. 4, fig. 7).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to modify the AAV8 vector comprising a nucleic acid sequence which encodes human C1 esterase inhibitor (C1EI) as disclosed in Adhi to select rAAV vector from serotype, rh10 or AAV 9 with modulator elements (promoter and polyA) as suggested in Hu in view of Sondh/ Ballantyne, in order to improve sustained expression of transgene in humans, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to use chicken beta actin promoter with rh.10 or AAV9 vector because this combination explicitly reported (i) the higher levels of transgene expression as compared to the commonly used other AAV capsid including AAV8 and (ii) the use of non-human primate (rhesus macaque)-derived AAV gene transfer vector such as rh.10 in humans would reduce pre-existing anti-vector immunity and (iii) combination of modular elements (CAG promoter and rabbit beta globin polyA) are reported to work well with AAVrh.10 (supra). One of skill in the art would have been expected to have a reasonable expectation of success because (i) all the recited elements were known in the art, and hence "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results as evident from the teaching of Adhi and (ii) prior art had successfully reported AAV rh10 or AAV9 provided the greatest level of expression as compared to AAV8 and all other serotypes following intravenous injection (see page 776, col. 1, para. , last para.).
Claims 1, 11, 13, 25, 31-32, 34-55 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Adhi et al (Investigative Ophthalmology & Visual Science, 2012, ARVO annual meeting abstract. 53; 1888), Hu et al (J Gene Med. 2010, 12(9): 766–778), Sondhi (Human Gene therapy methods, 2012, 23, 324-335)/ Ballantyne et al (PLoS One, 2015, 1-20) and further in view of Roeth et al (WO/2012/122025, dated 09/13/2012).
The teaching of Adhi, Hu, Sodhi et/ Ballantyne have been described above and relied in same manner here. The combination of reference differs from claimed invention by not disclosing (i) C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence.
Roeth cure the deficiency by disclosing vector encodes proteins comprising the amino acid sequence as set forth in SEQ ID NO: 10 (human Cl esterase inhibitor) that has 100% sequence homology with SEQ ID NO 1).
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Regarding Claim 13, 32, Roeth et al teach comprising pharmaceutically acceptable carrier and a vector containing human C1E1. (see para. 416, 417, 439). It is further disclosed that vector comprising a polynucleotide sequence encoding a human Cl esterase inhibitor (see para. 391-392, 468) to treat to treat angioedema, wherein said vector is an AAV vector (see para. 171-172, 475-478). Regarding claims 34-36, Roeth teaches contemplated using codon optimized coding sequence for expression in human (see para. 329, 331-337).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of prior art to substitute coding sequence of hC1esterase inhibitor disclosed in Adhi, Hu and Sodhi with one gene encoding hC1E1 protein or codon optimized hC1E1 sequence as disclosed in Roeth, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to use codon optimized the coding sequence encoding the hC1E1 protein for optimal use in in human as suggested in Roeth. One of skill in the art would have been expected to have a reasonable expectation of success because hC1E1 sequence was known in art and hence "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results as evident from the teaching of Adhi and (ii) prior art had successfully reported AAV rh10 provided the greatest level of expression followed by AAV9 as compared to all other serotypes including AAV8 following intravenous injection (see page 776, col. 1, para. , last para.). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith , --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR , 82 USPQ2d at 1396) (available at http: www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 6, 11, 13, 34 and 36 , are rejected under 35 U.S.C. 103 as being unpatentable over Sondhi (Human Gene therapy methods, 2012, 23, 324-335)/ Ballantyne et al (PLoS One, 2015, 1-20), Adhi et al (Investigative Ophthalmology & Visual Science, 2012, ARVO annual meeting abstract. 53; 1888), Hu (J Gene Med. 2010, 12(9): 766–778) and Roeth et al (WO/2012/122025, dated 09/13/2012).
Instant rejection is applied to the extent, claim reads on AAVrh10.
With respect to claim 1, 6., Sondhi teaches a recombinant AAVrh10 comprising an expression cassette comprising a chicken beta actin promoter, gene of interest and a rabbit beta globin polyA (see page 325, col. 1, para. 3). Likewise, Ballantyne teach generating AAVrh10 comprising chicken beta actin promoter operably linked to a coding sequence of gene of interest and rabbit-beta globin poly A to express higher level of gene of interest as compared to AAV8 (see page 5, para. 4, fig. 7). Sondhi et al provided the motivation to use AAVrh.10, an AAV isolated from rhesus monkeys, with the added advantage that it is nonhuman in origin, allowing it to bypass the anti-human AAV immunity that is common in the population (se page 325). Sondhi differs from claimed invention by not disclosing ) C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence.
Adhi et al teach an adeno-associated virus serotype 8 (AAV8) vector comprising a nucleic acid encoding human c-esterase inhibitor, wherein intravitreal injection result in sustained expression of hC1E1 (se abstract). The vector disclosed in Adhi is capable of producing hC1E1 because results show significant reduction in the leakage (see abstract) suggesting alleviating the deficiency of C1E1 that causes vascular leakage. The combination of references differs invention by not disclosing ) C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence. Hu teaches a composition comprising the AAV8, 9 and rh10 vector in a pharmaceutical acceptable carrier (phosphate buffered saline) (see 768, col. 1, para. 1). It is disclosed that AAV rh10 injected intravenously (see page 768, col. 1, para. 2) to the subject provided the greatest level of expression as compared to all other serotypes including AAV8 (see page 770, last para. page 771, col. 1, past para.). The combination of references differs from claimed invention by not disclosing (i) C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence.
Roeth cure the deficiency by disclosing vector encodes proteins comprising the amino acid sequence as set forth in SEQ ID NO: 10 (human Cl esterase inhibitor) that has 100% sequence homology with SEQ ID NO 1) (limitation of claim 11).
Regarding Claim 13, Roeth et al teach comprising pharmaceutically acceptable carrier and a vector containing human C1E1 (see para. 416, 417, 439). It is further disclosed that vector comprising a polynucleotide sequence encoding a human Cl esterase inhibitor (see para. 391-392, 468) to treat to treat angioedema, wherein said vector is an AAV vector (see para. 171-172, 475-478). Regarding claims 34, 36, Roeth teaches contemplated using codon optimized coding sequence for expression in human (see para. 329, 331-337).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of Sondhi/ Ballantyne by substituting the coding sequence of gene of interest with gene encoding hC1E1 protein or codon optimized hC1E1 sequence as disclosed in Adhi or Roeth, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to incorporate the coding sequence of hC1E1 in rAAVrh10 because prior art explicitly reported AAVrh10 provided the higher level of expression as compared to all other AAV serotype including AAV8 following intravenous injection. One of skill in the art would have been expected to have a reasonable expectation of success because hC1E1 sequence was known in art and hence (i) "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results as evident from the teaching of Sondhi/ Ballantyne and (ii) prior art had successfully reported use of AAV rh10 achieve greatest level of expression compared to all other serotypes including AAV8 following intravenous injection (see page 776, col. 1, para. , last para. Hu.). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith , --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR , 82 USPQ2d at 1396) (available at http: www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Claims 1, 6, 11, 13, 25, 31-32, and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Bosch et al (WO2015/173308, dated 11/19/2015, FD05/13/2015), Adhi et al (Investigative Ophthalmology & Visual Science, 2012, ARVO annual meeting abstract. 53; 1888), Roeth et al (WO/2012/122025, dated 09/13/2012) and Hu (J Gene Med. 2010, 12(9): 766–778).
Instant rejection is applied to the extent, claim reads on only AAV9.
With respect to claim 1, 6., Bosch teaches a recombinant AAV9 vector comprising an expression cassette comprising a CAG promoter comprising chicken beta actin, gene of interest (Naglu) and a rabbit beta globin polyA (see page 3, lines 21-25, example 2). Bosch further teaches using an optimized version of the coding sequence to produce protein in human subject (see example 3). Bosch further teaches a pharmaceutical composition comprising the recombinant AA V9 vectors in a pharmaceutically acceptable carrier (see page 26, lines 6-7).
Bosch differs from claimed invention by not disclosing C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence.
Adhi et al teach an adeno-associated virus serotype 8 (AAV8) vector comprising a nucleic acid encoding human c-esterase inhibitor, wherein intravitreal injection result in sustained expression of hC1E1 (se abstract). The vector disclosed in Adhi is capable of producing hC1E1 because results show significant reduction in the leakage (see abstract) suggesting alleviating the deficiency of C1E1 that causes vascular leakage. The combination of references differs invention by not disclosing ) C1E1 encodes a polypeptide comprising SEQ ID NO: 1 or C1E1 comprises a codon optimized sequence.
Roeth cure the deficiency by disclosing vector encodes proteins comprising the amino acid sequence as set forth in SEQ ID NO: 10 (human Cl esterase inhibitor) that has 100% sequence homology with SEQ ID NO 1) (limitation of claim 11, 31).
Regarding Claim 13, 32, Roeth et al teach comprising pharmaceutically acceptable carrier and a vector containing human C1E1. (see para. 416, 417, 439). It is further disclosed that vector comprising a polynucleotide sequence encoding a human Cl esterase inhibitor (see para. 391-392, 468) to treat to treat angioedema, wherein said vector is an AAV vector (see para. 171-172, 475-478). Regarding claims 34, 35, Roeth teaches contemplated using codon optimized coding sequence for expression in human (see para. 329, 331-337).
Therefore, it would have been prima facie obvious for a person of ordinary skill in the art to combine the teachings of Bosch by substituting the coding sequence of gene of interest with gene encoding hC1E1 protein or codon optimized hC1E1 sequence as disclosed in Adhi or Roeth, as instantly claimed, with a reasonable expectation of success, before the effective filing date of the instant invention. Said modification amounting to combining prior art elements according to known methods to yield predictable results. One of ordinary skill in the art would be motivated to use coding sequence encoding the hC1E1 protein in an AAV9 vector because prior art explicitly reported AAV9 provided the higher level of expression as compared to AAV8 following intravenous injection. One of skill in the art would have been expected to have a reasonable expectation of success because hC1E1 sequence was known in art and hence (i) "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results as evident from the teaching of Bosch and (ii) prior art had successfully reported use of AAV9 to provide higher level of expression as compared to AAV8 (see page 776, col. 1, para. , last para. of Hu.). It should be noted that the KSR case forecloses the argument that a specific teaching, suggestion, or motivation is required to support a finding of obviousness See the recent Board decision Ex parte Smith , --USPQ2d--, slip op. at 20, (Bd. Pat. App. & Interf. June 25, 2007) (citing KSR , 82 USPQ2d at 1396) (available at http: www.uspto.gov/web/offices/dcom/bpai/prec/fd071925.pdf).
Response to arguments
Applicants disagree with the rejection arguing that two new references were introduce to bolster its prior position regarding whether the claims are commensurate with evidence of unexpected results. The introduction of these references is not the result of Applicant’s claim amendments, and making the Office Action final while introducing new evidence deprives Applicant of a full and fair chance to rebut the evidence.
In response, as an initial matter, applicant should note that the two new references were not part of the rejection or any part of the statement of rejection. The references were made of record in direct response to applicant’s argument with specific statement that references are not being relied for the rejection. It is emphasized that only references that were part of the statement of rejection were relied for the rejecting the claim.
Applicant re-iterates prior arguments on pages 5 that are substantially the same as discussed in previous office action mailed on 04/10/2025. The arguments are substantially the same as those addressed in the prior office actions mailed on 04/25/2025 and incorporated herein. Examiner has simplified the rejection by splitting the rejection based on AAV of different serotype. To the extent that Applicants’ arguments are pertinent to new arguments, they are addressed as follows:
Applicant argues that the claims are directed to a novel and non-obvious gene therapy vector, not a method of treatment. Dose is not an element of the vector, nor does the Office provide any explanation of how a particular dose would be made an element of the claims. Furthermore, dose is not needed to render the claims commensurate in scope with the evidence of unexpected results. The data presented demonstrates that the expression level of the vector increases with increasing dose, and that the claimed vector can provide long term gene expression at high levels. These effects are the direct result of the novel and non-obvious combination of elements of the vector recited in the claims. Applicants’ arguments have been fully considered, but are not found persuasive.
In response, it is noted that applicant during the prosecution of instant application have extensively argued to the data both in the application (e.g., Figure 5D) and submitted via inventor’s Declaration on October 17, 2022 (e.g., page 5) asserting that clinically relevant levels of C1EI was delivered over 24 weeks using certain AAV vectors, including AAV.rh10 and AAV9. However, pending claims do not require any relevant level of C1EI for any duration using the claimed AAV vectors. The independent claims simply recite the structure of AAV vector. Thus, applicant’s argument that claimed vector exhibit unexpected superior expression is not commensurate with the scope as no level of expression for any duration is required by the claims It is not the vector but it is the composition comprising a therapeutically effective amount of a recombinant adeno-associated virus (AAV) vector of the invention that is capable of producing human C1E1 expression and/or activity is greater than the clinical threshold value for 6 weeks after the composition is administered to a mammal. For example, a composition comprising 10*10gc of AAVrh10 comprising the claimed expression cassette in female did not yield a clinically relevant level of human C1E1 activity for sustained period as previously argued by applicant. These results clearly indicate criticality of vector dosage in the composition affects the resulting hC1E1 activity (see fig. 4B) (emphasis added) (see below for AAVrh10C1E1 10*10gc below clinical threshold level and no sustained hC1E1 expression). These results suggest that vector alone is not capable of showing unexpected superior expression as argued by the applicant.
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To the extent that Sondhi / Ballantyne or Bosch describe a recombinant AAV9 or AAVrh10 vector comprising the modular element ( a chicken beta actin, gene of interest and a rabbit beta globin polyA) that is structurally similar to one claimed in the instant application, the rejection is applicable to the instant case.
On pages 6-7 of the applicant’s argument, applicant argues that codon optimization is not critical and codon optimization is a routine technique most often used for expressing proteins that are not native to the host. Here, the data presented involved the expression of a human C1 esterase inhibitor in a mouse model, such that codon optimization was appropriate. However, the particular codon-optimized sequenced used for expression in the mouse would not be applicable to the human therapy for which the vector is designed. Indeed, it is well known that expression of human proteins in a human host would not likely benefit much, if at all, from codon-optimization. Applicants’ arguments have been fully considered, but are not found fully persuasive.
In response, Examiner would agree with applicant’s assertion that codon optimization is a routine technique most often used for expressing proteins that are not native to the host. Previous office action merely asserted that dosage of viral vector, route of administration, viral capsid, viral genome, coding sequence and modular elements (promoter, enhancer and polyA) all play a crucial role in influencing gene expression (emphasis added). It is in this context; it was indicated that claims are not limited to a finite or specific engineered codon optimized sequence. It is generally known in art that not all codon optimized sequence increase gene expression at same level, therefore give that the breadth of claims that encompass a large number of unidentified, unpredictable codon optimized solutions and one of ordinary skill in the art would have predictably selected out of the innumerable sequences available within the genus of codon optimized sequence for expression in human cells using techniques well known in prior art. Examiner has provided adequate evidence to show that each of the modular elements (promoter and polyA sequences) in the claimed AAV vectors were known in prior art to function in obvious manner in enhancing gene expression of while designing/ modifying the rAAVrh10 or rAAV9 vector as evident form the teaching of Sondhi/Ballantyne, Bosch in view of Hu.
Therefore, in view of the fact patterns of the instant case, and the ground of rejection outlined by the examiner, applicants’ arguments are not compelling and do not overcome the rejection of record.
Conclusion
No claims allowed.
Niwa et al. (Gene, 108: 193-199, 1991) reported testing efficiency of different promoter elements for the construction of expression vector that enhances the level of expression of the linked exogenous gene. The results show CAG promoter showed highest activity as compared to CMV and RSV (see table 1).
Shin et al (Methods Mol Biol. 2012; 798: 267–284) teaches generic AAV production and purification protocol.
Guo teaches higher A1AT transgene expression using AAV8 as compared to other AAV serotypes.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached on (571)272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ANOOP K SINGH/Primary Examiner, Art Unit 1632