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 .
Claim Status
Applicant’s amendment filed 09/16/2026 has been received and entered. Claims 1-11, 13-16, 18-22, 24-25 and 34 have been amended. Claims 22-34 remain withdrawn as being directed to non-elected inventions. Accordingly, claims 1-11, 13-16 and 18-21 are pending and under current examination.
Status of Prior Rejections/Response to Arguments
The objection to claim 16 is maintained:
Applicant’s amendment to claim 16 does not replace the “(a)” and “(h)” in line 1 with “a)” and “h)”. The objection is maintained.
The rejection to claims 1, 3, 6, 8, 10-13, 16 and 18-19 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al. is maintained:
Applicant has traversed the rejection, asserting that there is nothing in Alam and Kotin that would lead one of skill in the art to the claimed invention, particularly the use of only one GIRE in the recombinant AAV8 vector (Remarks, p6). Alam recites that the vector preferably requires "2-4 GIREs, most preferably 3 GIREs”, Kotin does not mention GIREs. Therefore, a skilled artisan would have no motivation to use only one GIRE as claimed, nor could they have reasonably expected the surprising benefits associated therewith based on a reading of the cited references (Remarks, p6).
Applicant’s arguments are fully considered but they are not persuasive. Applicant is reminded that "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). With that, a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, even nonpreferred embodiments. See MPEP § 2123: Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989); Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005). In the instant case, Alam et al. teach the vector of the invention requires 1-5 GIREs (see parag 0053), which includes only one GIRE in the vector. Therefore an ordinary skill in the art would have been reasonably apprised of using only one GIRE in the vector. The rejection is maintained in modified form to address amended limitations.
The rejection to claims 1-3, 6, 8, 10-13, 16 and 18-19 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al., further in view of Choi et al. is maintained:
The rejection to claims 1, 3, 4, 6-8, 10-14, 16 and 18-19 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al., further in view of Alam-441, evidenced by GenBank: M12523.1 is maintained:
The rejection to claims 1, 3, 5, 6, 8-13, 16 and 18-19 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al., further in view of Alam-972 is maintained:
The rejection to claims 1, 3, 6, 8, 10-13, 15-16 and 18-19 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al., further in view of Ling et al. is maintained:
The rejection to claims 1, 3, 6, 8, 10-13, 15-16, 18-19 and 20-21 under 35 U.S.C. 103 over Alam et al. in view of Kotin et al., further in view of Qiao et al. is maintained:
Applicant has further traversed the rejection, asserting that Choi et al., Ling et al. and Qiao et al. do not teach GIREs, Alam-441 teaches the vector preferably requires “2-4 GIREs, most preferably 3 GIREs” (Remarks, p7), and Alam-972 teaches away from using only one GIRE, reciting that “glucose dependent expression and secretion of insulin in cells transfected with AdISMA2B, which contains a single GIRE, was minimal” (Remarks, p7), therefore one of skill in the art would not be motivated to use only one GIRE based on the teachings.
In response, the Examiner respectfully submits that as discussed above, nonpreferred embodiments constitute prior art. Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). Moreover, Applicant is reminded that the asserted functionality (herein the glucose dependent expression and secretion of insulin) is not required by, nor recited within, the pending composition claims. Although the claims are interpreted in light of the Specification, limitations from the Specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Thus, the composition of Alam et al. as modified by Kotin et al. need not render obvious the same functions. The rejection is maintained in modified form to address amended limitations.
Modified Rejections
Claim Interpretation
Instant claim 2 recites “the 5’ ITR is SEQ ID NO: 2”. Since the claim does not use transitional phrases such as “comprising” or “consisting of”, the Examiner provides the broadest reasonable interpretation (BRI) to the claim as the 5’ ITR comprising SEQ ID NO: 2 for the search of the prior art. Similarly, claims 4, 5, 7, 9 and 14-15 are also interpreted as comprising the recited SEQ ID NOs.
Modified Claim Objections
Claim 16 is objected to because of the following informalities: Claim 16 recites “(a)” and “(h)” in line 1, they should be “a)” and “h)”. Appropriate correction is required.
Modified 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.
Claims 1, 3, 6, 8, 10-13, 16 and 18 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS). The rejection is modified as necessitated by Applicant’s amendment.
Alam et al. teach vectors for controlling blood glucose levels in a mammal (Abstract).
Regarding claim 1, Alam et al. teach a vector comprises (parag 0047): a promoter enhancer (parag 0048), a glucose inducible regulatory element (GIRE) (see parag 0053, require 1-5 GIRES), a liver specific promoter (parag 0055), a translational enhancer (parag 0051), a gene encoding Insulin with modified peptidase site (parag 0058) and an Albumin 3’UTR (parag 0065), which reads on the components b), c), d), e), f), and g), as well as the limitation of one GIRE as recited in instant claim.
Alam et al. do not teach a) a 5' inverted terminal repeat (ITR) and h) a 3' ITR. However, it was disclosed by Kotin et al. at the time of instant invention.
Kotin et al. teach an improved production of a non-viral capsid-free DNA vector with covalently-closed ends (referred to herein as a "closed-ended DNA vector" or a "ceDNA vector") (parag 0011).
Regarding claim 1, Kotin et al. teach a nucleic acid construct for the production of DNA vectors, e.g., ceDNA vectors (a non-viral capsid-free DNA vector with covalently-closed ends), and other recombinant parvovirus (e.g. adeno associated virus) vectors in cells (e.g. insect cells, mammalian cells) and cell free systems (parag 0013). In some embodiments the ceDNA genome is incorporated as an intermolecular duplex polynucleotide of DNA into a plasmid or viral genome (parag 0086). Kotin et al. teach a pair of modified-ITRs within a single ceDNA genome or ceDNA vector that are both that have an inverse complement sequence across their entire length (parag 0084). The pair of ITRs reads on a) a 5' inverted terminal repeat (ITR) and h) a 3' ITR as recited in instant claims.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al.’s recombinant AAV8 vector, and add a pair of inverted terminal repeat (ITR) in the vector as taught by Kotin et al.. The skilled artisan would have been motivated to use the 5’ ITR and 3’ ITR in the vector for the production of recombinant AAV (i.e., AAV8) since Kotin et al. teach ITRs mediate replication, virus packaging, integration and provirus rescue (parag 0078). There would be a reasonable expectation of success of having a pair of inverted terminal repeat (ITR) in the vector since Kotin et al. teach ITRs for AAV (i.e., AAV8, see parag 00193).
Regarding claim 3, Alam et al. teach the “promoter enhancer” they use are alpha-fetoprotein enhancer (see parag 0048, and Example 1).
Regarding claim 6, Alam et al. teach the promoter in the vector is preferably an albumin promoter (see parag 0055, and Example 1).
Regarding claim 8, Alam et al. teach the translational enhancer in the vector is the VEGF translational enhancer (see parag 0051).
Regarding claim 10, Alam et al. teach in Example 1, human insulin cDNA sequence was modified at B-C and C-A junction for furin cleavage compatibility so that liver cells are able to process preproinsulin to functional insulin (parag 0085).
Regarding claims 11 and 13, Alam et al. teach the vectors of the invention comprise a gene encoding insulin, preferably human insulin or non-human mammalian insulin, with a modified peptidase site (parag 0058). To ensure that no immune reaction to insulin occurs when diabetic animals, such as cats or dogs, are treated using insulin gene therapy, one would use species-specific insulin in
minicircle DNA for treating animals (parag 0059). This teaching reads on dog or cat insulin with a modified peptidase site (claim 11) or human insulin with a modified peptidase site (claim 13).
Regarding claim 16, following the discussion above, Alam et al. teach a gene construct in Example 1 (parag 0085): the construct contains various elements in (5’-3’) order as: AFP-enhancer, GIRE(s), Alb-promoter, HGH-intron, human insulin and Alb 3’ UTR. Kotin et al. teach a 5' ITR and a 3' ITR, which are located 5’ to (upstream of) the expression cassette (construct) and 3’ (downstream of) the expression cassette (see parag 0078). It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al.’s vectors having components in 5’-3’ order: AFP-enhancer, GIRE(s), Alb-promoter, HGH-intron, human insulin and Alb 3’ UTR, add a pair of inverted terminal repeat (ITR) in the vector as taught by Kotin et al. and locate the ITRs upstreaming and downstream of the vector, respectively. The skilled artisan would have been motivated to use the 5’ ITR and 3’ ITR at the 5’ end and 3’ end respectively in the vector for the production of recombinant AAV (i.e., AAV8) since Kotin et al. teach ITRs mediate replication, virus packaging, integration and provirus rescue (parag 0078). There would be a reasonable expectation of success of having a pair of inverted terminal repeat (ITR) in the 5’ end and 3’ end of vector since Kotin et al. teach ITRs for AAV8 (i.e., parag 00193).
Regarding claim 18, Alam et al. teach introduction of the insulin expression constructs into liver cells can be achieved either in vivo or ex vivo (parag 0079). The liver cells are the host cell transduced with the construct as recited in instant claim.
Claims 1-3, 6, 8, 10-13, 16 and 18 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16, 18 above, further in view of Choi et al. (US 20210275614 A1, 371 of PCT/US19/57916 with a PCT filing date of 10/29/2019). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claim 2, Alam et al. and Kotin et al. do not teach the sequence of 5' ITR is SEQ ID NO: 2. However, this was disclosed by Choi et al. at the time of instant invention.
Choi et al. teach a triple-plasmid system for producing recombinant adeno-associated viruses (Abstract).
Regarding claim 2, Choi et al. teach a 5′ ITR (e.g., SEQ ID NOs: 2 or 43) (parag 0023). Herein the SEQ ID NO:43 is 100% identical to SEQ ID NO:2 in instant claim (sequence alignment is provided).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al. in view of Kotin et al.’s vectors having 5’ITR, and use the sequence of 5′ ITR as taught by Choi et al.. The only difference between instant claim and Alam et al. in view of Kotin et al.’s vector is instant claim have a different sequence of 5’ ITR. Given that Kotin et al. teach ITRs mediate replication, virus packaging, integration and provirus rescue (parag 0078), and Choi et al. teach the sequence of 5′ ITR, one of ordinary skill in the art would have substituted Alam et al. in view of Kotin et al.’s 5’ ITR sequence for Choi et al.’s 5’ ITR sequence depends on their research interest and preference. This simple substitution of one known element (Choi et al.’s ITR sequence) for another known element (Alam et al. in view of Kotin et al.’s ITR) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3, 4, 6-8, 10-14, 16 and 18 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16, 18 above, further in view of Alam et al. (US 2017/0342441 A1, published in 2017, herein after “Alam-441”), evidenced by GenBank: M12523.1 (available 1986). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claims 4, 7 and 14, Alam et al. and Kotin et al. do not teach the sequence of alpha-fetoprotein enhancer is SEQ ID NO: 3, the albumin promoter is SEQ ID NO: 5, and albumin 3' UTR is SEQ ID NO: 8. However, such was disclosed by Alam-441 at the time of instant invention.
Alam-441 teaches a method and vectors for controlling blood glucose levels in a mammal (Abstract).
Regarding claim 4, Alam-441 teaches a promoter enhancer is residues 15 - 265 of SEQ ID NO : 1 (p13, left column). Herein the residues 15 - 265 of SEQ ID NO : 1 is 100% identical to SEQ ID NO: 3 in instant claim (sequence alignment is provided).
Regarding claim 7, Alam-441 teaches the albumin promoter is residues 380 - 706 of SEQ ID NO : 1 (p12, right column). Herein the residues 380 - 706 of SEQ ID NO : 1 is 100% identical to SEQ ID NO: 5 in instant claim (sequence alignment is provided).
Regarding claim 14, Alam-441 teaches albumin 3 ' UTR is residues 1204 - 2077 of SEO ID NO : 1 (p12, right column). Herein the residues 1204 - 2045 of SEQ ID NO : 1, which are within the residues 1204 - 2077, also cover the complete cds of human serum albumin (ALB) gene (at region 18372..18975, evidenced by GenBank: M12523.1) is 100% identical to SEQ ID NO: 8 in instant claim (sequence alignment is provided).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al.’s vectors for controlling blood glucose levels in a mammal, and use the sequence of alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR as taught by Alam-441. The only difference between instant claim and Alam et al.’s vectors is instant claim use a different sequence of alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR. Given that Alam-441 teaches the sequence of alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR, one of ordinary skill in the art would have substituted Alam et al.’s alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR for Alam-441’s sequence of alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR depends on their research interest and preference. This simple substitution of one known element (Alam-441’s sequence of alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR) for another known element (Alam et al.’s alpha-fetoprotein enhancer, albumin promoter and albumin 3 ' UTR) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3, 5, 6, 8-13, 16 and 18 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16, 18 above, further in view of Alam et al. (US 20050265972 A1, published in 2005, herein after “Alam-972”). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claims 5 and 9, Alam et al. and Kotin et al. do not teach the sequence of the GIRE is SEQ ID NO: 4, as well as the VEGF translational enhancer is SEQ ID NO: 6. However, this was disclosed by Alam-972 at the time of instant invention.
Alam-972 teaches a method for obtaining glucose-regulated expression of active insulin in the cells of a mammalian subject (Abstract).
Regarding claim 5, Alam-972 teaches regulatory modules having one (SEQ ID NO:8) GIRE (parag 0045). Herein the SEQ ID NO: 8 is 100% identical to SEQ ID NO: 4 in instant claim (sequence alignment is provided).
Regarding claim 9, Alam-972 teaches the translational enhancer comprises residues 310-472 of SEQ ID NO:25 (p20, right column). Herein the residues 309/310-472 of SEQ ID NO:25 is 100% identical to SEQ ID NO: 6 in instant claim (sequence alignment is provided).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al.’s vectors for controlling blood glucose levels in a mammal, and use the sequence of GIRE and VEGF translational enhancer as taught by Alam-972. The only difference between instant claim and Alam et al.’s vectors is instant claim use a different sequence of GIRE and VEGF translational enhancer. Given that Alam-972 teaches sequence of GIRE and VEGF translational enhancer, one of ordinary skill in the art would have substitute Alam et al.’s GIRE and VEGF translational enhancer for Alam-972’s sequence of GIRE and VEGF translational enhancer depends on their research interest and preference. This simple substitution of one known element (Alam-972’s sequence of GIRE and VEGF translational enhancer) for another known element (Alam et al.’s GIRE and VEGF translational enhancer) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3, 6, 8, 10-13, 15-16 and 18 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16 and 18 above, further in view of Ling et al. (US 2021/0139933 A1, filed in 2020). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claim 15, Alam et al. and Kotin et al. do not teach the sequence of the 3' ITR is SEQ ID NO: 9. However, this was disclosed by Ling et al. at the time of instant invention.
Ling et al. teach methods and compositions for the treatment of diseases and genetic disorders linked to SURF1 loss and/or misfunction. The methods and compositions comprise rAAV vectors and rAAV viral vectors comprising transgene nucleic acid molecules comprising nucleic acid sequences encoding for a SURF1 polypeptide. (Abstract).
Regarding claim 15, Ling et al. teach an AAV ITR sequence comprises a nucleic acid sequence set forth in SEQ ID NO: 12 (parag 0013) which is 100% identical to SEQ ID NO: 9 in instant claim..
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al. in view of Kotin et al.’s vectors having 3’ITR, and use the sequence of 3′ ITR as taught by Ling et al.. The only difference between instant claim and Alam et al. in view of Kotin et al.’s vector is instant claim have a different sequence of 3’ ITR. Given that Kotin et al. teach ITRs mediate replication, virus packaging, integration and provirus rescue (parag 0078), and Ling et al. teach the sequence of 3′ ITR, one of ordinary skill in the art would have substituted Alam et al. in view of Kotin et al.’s 3’ ITR sequence for Ling et al.’s 3’ ITR sequence depends on their research interest and preference This simple substitution of one known element (Ling et al.’s ITR sequence) for another known element (Kotin et al.’s ITR) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3, 6, 8, 10-13, 16 and 18 stand and claim 19 is newly rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16 and 18 above, further in view of Ferreri et al. (US 10,378,055 B2, patented in 2019). The rejection is necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claim 19, Alam et al. and Kotin et al. do not teach the polynucleotide encoding insulin has at least 80% sequence identity to SEQ ID NO: 7 or has at least 80% sequence identity to the coding region of SEO ID NO: 10. SEQ ID NO: 11, SEQ ID NO: 12. or SEQ ID NO: 13. However, this was disclosed by Ferreri et al. at the time of instant invention.
Ferreri et al. teach nucleic acids, methods, and kits for detecting unmethylated DNA in body fluid sample of a subject (Abstract).
Regarding claim 19, Ferreri et al. teach human Insulin gene (SEQ ID NO:13) (Col 15). The SEQ ID NO:13 is 100% identical to SEQ ID NO:13 in instant claim (sequence alignment is provided below).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al. in view of Kotin et al.’s recombinant AAV8 vector, and have the polynucleotide encoding insulin has sequence 100% identical to SEQ ID NO: 13 (human insulin gene) as taught by Ferreri et al. The only difference between instant claim and Alam et al. in view of Kotin et al.’s recombinant AAV8 vector is instant claim has the polynucleotide encoding insulin has at least 80% sequence identity to SEQ ID NO: 7 or has at least 80% sequence identity to the coding region of SEO ID NO: 10. SEQ ID NO: 11, SEQ ID NO: 12. or SEQ ID NO: 13. Given that Alam et al. requires a polynucleotide encoding insulin, and Ferreri et al. teach the sequence of human insulin gene, one of ordinary skill in the art would have substituted Alam et al.’s polynucleotide encoding insulin gene, and used Ferreri et al.’s sequence of human insulin gene. This simple substitution of one known element (Ferreri et al.’s sequence of human insulin gene) for another known element (Alam et al.’s polynucleotide encoding insulin gene) is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 — 97 (2007) (see MPEP § 2143, B.).
Claims 1, 3, 6, 8, 10-13, 16, 18 and 20-21 stand rejected under 35 U.S.C. 103 as being unpatentable over Alam et al. (WO 2012/170531 A1, published in 2012, cited in IDS) in view of Kotin et al. (WO 2020/168222 A1, published in 2020, cited in IDS), as applied to 1, 3, 6, 8, 10-13, 16 and 18 above, further in view of Qiao et al. (J Virol. 2002 Feb;76(4):1904-13). The rejection is modified as necessitated by Applicant’s amendment.
The teaching of Alam et al. and Kotin et al. is set forth above.
Regarding claims 20-21, Alam et al. and Kotin et al. do not teach a packaging cell line for producing the virus particle, and the cell line comprises the complement of any genes functionally deleted in the virus particle. However, this was disclosed by Qiao et al..
Qiao et al. explored the feasibility of creating inducible AAV packaging cell lines that require neither transfection nor helper virus infection (Abstract).
Regarding claims 20-21, Qiao et al. teach cell line containing highly inducible Ad E1A and E1B genes, which are essential for AAV production. Subsequently, the AAV Rep and Cap genes and an AAV vector containing a green fluorescent protein (GFP) reporter gene were stably introduced into the E1A-E1B cell line, generating inducible AAV-GFP packaging cell lines. Upon induction of E1A and E1B genes and infection with replication-defective Ad with E1A, E1B, and E3 deleted, the packaging cells yielded high-titer AAV-GFP vectors ((Abstract). Herein the E1A-E1B cell line is packaging cell line for AAV, and the cell line comprises the complement of genes functionally deleted in the virus particle such as Ad E1A and E1B genes, this cell line is effective for AAV packaging and producing since the cells yielded high-titer AAV-GFP vectors.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify Alam et al.’s vectors for controlling blood glucose levels in a mammal, and have a packaging cell line for producing AAV virus, and the packaging cell line comprises the complement of genes functionally deleted in the virus particle (i.e., E1A gene) as taught by Qiao et al.. The skilled artisan would have been motivated to have a AAV packaging cell line comprises the complement of genes functionally deleted in the virus particle (i.e., E1A gene) since Qiao et al. teach using such AAV packaging cell eliminated the tedious transient-transfection step as well as the
requirement for wt Ad helper infection (p1905, left column) and still be able to obtain high-titer of AAVs. There would be a reasonable expectation of success of having such packaging cell lines since Qiao et al. teach the method of making such packaging cell lines (see p1905, Materials and Methods).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 QINHUA GU whose telephone number is (703)756-1176. The examiner can normally be reached M-F: 9:00 - 5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher Babic can be reached at (571)272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Q.G./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
Sequence Alignment
SEQ ID NO:13 in instant application v.s. SEQ ID NO:13 in Ferreri et al. (US 10,378,055 B2)
PNG
media_image1.png
92
726
media_image1.png
Greyscale
PNG
media_image2.png
828
761
media_image2.png
Greyscale
PNG
media_image3.png
752
763
media_image3.png
Greyscale
PNG
media_image4.png
316
751
media_image4.png
Greyscale
Prosecution Insights