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 .
Applicants’ arguments and amendments to the claims filed on response to restriction requirement filed on June 9, 2026 have been received and entered. Claims 1, 16, 19 and 20 have been amended, while claims 2-4, 8-15 have been canceled. Claims 1, 16-22 are pending in the instant application.
Election/Restrictions
Applicant’s election without traverse of claims 1-4, 8-21 (group I) in the reply filed on November 12, 2025 was acknowledged.
Claim 22 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 12, 2025.
Priority
This application is a Continuation of PCT/CN2022/117383 filed on 09/06/2022, which claims priority from foreign application PCTCN2021116781 filed on 09/06/2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Objections
Claim 18 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claims 1, 16-20 and 21 are under consideration.
Withdrawn-Claim Rejections - 35 USC § 112
Claims 1-4, 8-17, 19-20 and 21 were 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. Applicant’s amendments to the claims obviates the basis of the rejection.
Withdrawn-Claim Rejections - 35 USC § 102
Claims 1-4, 8, 12-13 and 19 were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tian (CN108103096, dated 06/01/2018, IDS) as evidenced by Wang (Molecular Therapy, 2018, 9, 234-246). Applicants’ cancellation of claims 2-4, 8, 12-13 renders their rejections moot. In view of Applicants’ amendment of base claim 1, introducing the limitation “of claim 16 that is not taught by Tian., the previous rejection is rendered moot and hereby withdrawn. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1-4, 8-9, 12-13, 15, were rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sun (CN111118017, dated 08/05/2020, IDS). Applicants’ cancellation of claims 2-4, 8-9, 12-13 renders their rejections moot. In view of Applicants’ amendment of base claim 1, introducing the limitation “of claim 16 that is not taught by Tian., the previous rejection is rendered moot and hereby withdrawn. The claims are however subject to new rejections over the prior art of record, as set forth below.
Withdrawn-Claim Rejections - 35 USC § 103
Claims 1-4, 8-15, 19 and 21 were rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS). Zhang et al (CN109402244, dated 06/27/2019), Tang et al (US US20090215178, 8/27/2009) and Wang (Molecular Therapy, 2018, 9, 234-246). Applicants’ cancellation of claims 2-4, 8-9, 12-1, 15 renders their rejections moot. In view of Applicants’ amendment of base claim 1, introducing the limitation “of claim 16 that is not taught by Tian., the previous rejection is rendered moot and hereby withdrawn. The claims are however subject to new rejections over the prior art of record, as set forth below.
Claims 1, 19 and 20 rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS) as evidenced by Wang (Molecular Therapy, 2018, 9, 234-246) as applied above for claim 1 and further in view of Kay (USPGPUB 20070243526). In view of Applicants’ amendment of base claim 1, introducing the limitation “of claim 16 that is not taught by the combination of references, the previous rejection is rendered moot and hereby withdrawn. The claims are however subject to new rejections over the prior art of record, as set forth below.
New-Modified Claim Rejections - 35 USC § 103- necessitated by amendments
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, 16, 17 remain rejected and claims 19 and 21 are newly rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS). Zhang et al (CN109402244, dated 06/27/2019), Tang et al (US US2009215178, 8/27/2009), Wang (Molecular Therapy, 2018, 9, 234-246) as applied above and further in view of Banfi (US10369231, 6/8/2019) and Zhou et al (CN106636409A, 10/5/2017).
With respect to claim 1, Sun teaches a rAAV particle comprising an AAV9 serotype comprising cap gene and a vector encoding an hRPE65 polypeptide (see para. 37, 39, 130 and 90, 92, claim 5). Sun teaches vector comprises a left ITR sequence; a ubiquitous promoter, an optimized human RPE65 encoded sequence; a human growth hormone (hGH polyA); and a right ITR sequence (see para. 42-47) and wherein the coding sequence of human RPE65 comprises SEQ ID NO: 2 that has 97% sequence identity to SEQ ID NO: 2 (see sequence search report). Sun teaches 5’ITR a 3’ ITR having SEQ ID NO: 4 that contains nt 1-141 that has 100% sequence identity to SEQ ID NO: 7 and nucleotides 4015 to 4155 that has 100% sequence identity to SEQ ID NO: 8 respectively (see para. 43). Sun further teaches the promoter is a CAG promoter (see para. 139). Sun teaches that polyA signal sequence is human GH poly sequence (see para. 29, 46). Sun teaches that vector genome comprises a kozak sequence from nucleotides 951 to 956 of SEQ ID NO: 4 that has 100% sequence identity to SEQ ID NO: 6 (see para. 143 and 183 and sequence search below).
Query Match 100.0%; Score 6; DB 1; Length 6752;
Best Local Similarity 100.0%;
Matches 6; Conservative 0; Mismatches 0; Indels 0; Gaps
Qy 1 GCCACC 6
||||||
Db 951 GCCACC 956
Regarding claim 21, Sun teaches a pharmaceutical composition comprising a rAAV particle comprising an AAV9 serotype complete cap gene and a vector encoding an hRPE65 polypeptide (see para. 37, 39, 130 and 90, 92, claim 5) and an excipient (see para. 149-152). Likewise, Tian teaches a viral particle comprising an AAV9 serotype comprising cap gene and a vector encoding an hRPE65 polypeptide (see para. 47 and 92). Tian teaches that vector genome comprises a 5’AAV3 ITR, an RPE polynucleotide encoding RPE65, a bGH polyA sequence and an AAV2 3’ITR (see para. 55-59, fig. 1-3). It is noted that Tian teaches hRPE encoded by nucleic acid sequence as set forth in SEQ ID NO: 5 that has 99% sequence identity to SEQ ID NO: 2 (see claim 1, SEQ IDNO: 5) (see sequence search result).
With respect to claim 1, Tian teaches a viral particle comprising an AAV9 serotype comprising cap gene and a vector encoding an hRPE65 polypeptide (see para. 47 and 92). Tian teaches that vector genome comprises a 5’AAV3 ITR, an RPE polynucleotide encoding RPE65, a CMV early promoter operably linked to the RPE65 nucleotide, a bGH polyA sequence and an AAV2 3’ITR (see para. 55-59, fig. 1-3). It is noted that Tian teaches hRPE encoded by nucleic acid sequence as set forth in SEQ ID NO: 5 that has 99% sequence identity to SEQ ID NO: 2 (see claim 1, SEQ IDNO: 5) (see sequence search result). Tian teaches that the promoter is a ubiquitous promoter such as a CMV enhancer and/or promoter (see para. 51, fig. 1-2).
Regarding claim 19, Tian teaches that the AAV9 serotype comprises all the cap gene that would inherently include AAV9 VP1, VP2 and VP3 (para. 47) as evident form the teaching of Wang (see VP1, VP2, and VP3 at 1:1:10 ratio in wild type AAV9 see 235, col. 1, para. 2).
While combination of references teach vector genome from 5' ITR to 3' ITR included a human RPE65 coding sequence that is at least 99% sequence identity to SEQ ID NO: 2 encoding human RPE65 polypeptide, a CAG promoter operably linked to the human RPE65 coding sequence, a bGH polyA sequence downstream of the human RPE65 coding sequence, flanked by a 5' ITR (SEQ ID NO: 7) and a 3' ITR (SEQ ID NO: 8), which are derived from AAV2, but differs from claimed invention by not disclosing use of ubiquitous promoter CAG as set forth in SEQ ID NO: 4, hGH poly sequence as set forth in SEQ ID NO: 5 and use of a Kozak sequence upstream of and immediately 5' to the human RPE65 coding sequence as set forth in SEQ ID NO: 2.
Zhang cure the deficiency by providing requisite sequence of CAG promoter as set forth in nt 801 to 2472 of SEQ ID NO: 2 that has 100% sequence identity to SEQ ID NO: 4 (see SEQ ID NO: 2, claim 5 of ‘244), while Tang teaches SEQ ID NO: 30 that has 100% sequence identity to hGH polyA (see example 3, SEQ ID NO: 30). The combination of references differs from claimed invention by not disclosing use of a Kozak sequence upstream of and immediately 5' to the human RPE65 coding sequence.
Prior to instant invention, Wang teaches AAV capsid consists of 60 copies of viral protein (VP) subunits, with VP1, VP2, and VP3 at 1:1:10 ratio (see 235, col. 1, para. 2). Wang teaches Kozak sequence (GCCACC) is added upstream of the start codon sequence of coding sequence to enhance gene expression (see page 242, col. 2, para. 2).
While combination of references teach AAV9 comprising AAV9 capsid and a vector genome comprises a human RPE65 coding sequence that is at least 99% sequence identity to SEQ ID NO: 2 encoding human RPE65 polypeptide, a CAG promoter operably linked to the human RPE65 coding sequence, a bGH polyA sequence downstream of the human RPE65 coding sequence, flanked by a 5' ITR (SEQ ID NO: 7) and a 3' ITR (SEQ ID NO: 8), which are derived from AAV2, but differs from claimed invention by not disclosing RPE65 coding sequence is SEQ ID NO: 2 .
Before the effective filing date of instant invention, use of recombinant expression vector comprising one or more wild-type form of a coding sequence responsible for the retinal dystrophy under the control of a suitable promoter or use in the treatment and/or prevention of a retinal dystrophy, wherein one or more coding sequence include SEQ ID NO: 37 that has 100% sequence identity to SEQ ID NO: 2 of instant application (see col. 6, lines 43-46. . 49-51, claims 6, 7 of ‘231).
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 AAV comprising AAV9 capsid and vector genome encoding human RPE65 as disclosed in Sun/Tian with structurally and functionally equivalent human RPE65 coding sequence as disclosed in Banfi, as instantly claimed, with a reasonable expectation of success, before the effective filing date of instant application. 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 do so because prior art explicitly reported using wild type human RPE65 coding sequence for therapeutic purpose in human subject. Further , prior art explicitly reported use of CAG promoter and hGH polyA together function well as evident from the teaching of Sun and Thian. Other limitation of vector genome having a sequence that is at least 99% to SEQ ID NO: 1 would be obvious modification particularly since combination of prior art teaches the same 5’ITR of SEQ ID NO:7, a CAG promoter of SEQ ID NO:4, a linker box sequence, Kozak sequence, a hRPE sequence as set forth in SEQ ID NO: 2, a hGH polyA of SEQ ID NO: 5 and a3’polyA ITR of SEQ ID NO: 8 as one recited in claim 16 and 17 and therefore resulting combined sequence would be at least 99.4% of SEQ ID NO:1. Absent any unexpected superior results, one of skill in the art would have been expected to have a reasonable expectation of success in using the claimed sequence of CAG, hGH polyA and human RPE65 within the AAV construct because prior art teaches the successful use of these promoter, coding and polyA sequences within AAV vector for enhanced gene expression in ocular cells. 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, 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN111118017, dated 08/05/2020, IDS), Tian (CN108103096, dated 01/06/2018, IDS). Zhang et al (CN109402244, dated 06/27/2019), Tang et al (US US2009215178, 8/27/2009), Wang (Molecular Therapy, 2018, 9, 234-246) , Banfi (US10369231, 6/8/2019) and Zhou et al (CN106636409A, 10/5/2017).as applied above for claim 1 and further in view of Kay (USPGPUB 20070243526).
The teaching of Sun/Tian, Zhang, Tang, Wang, Banfi and Zhou have been described above and relied in same manner here. While combination of references teaches a rAAV virus particle comprising AAV9 serotype comprising all the cap gene that inherently includes VP1, VP2 and VP3 as evidenced by Wang but differs from claimed invention by not disclosing AAV9 serotype capsid comprises AAV9 VP1 as set forth in SEQ ID NO: 9.
Kay provides the requisite sequence of AAV9 VP1 as set forth in SEQ ID NO: 5 that has 100% sequence identity to SEQ ID NO: 9 (see sequence search result).
Query Match 100.0%; Score 3986; Length 736;
Best Local Similarity 100.0%;
Matches 736; Conservative 0; Mismatches 0; Indels 0; Gaps
Qy 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAADGYLPDWLEDNLSEGIREWWALKPGAPQPKANQQHQDNARGLVLPGYKYLGPGNGLD 60
Qy 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 KGEPVNAADAAALEHDKAYDQQLKAGDNPYLKYNHADAEFQERLKEDTSFGGNLGRAVFQ 120
Qy 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AKKRLLEPLGLVEEAAKTAPGKKRPVEQSPQEPDSSAGIGKSGAQPAKKRLNFGQTGDTE 180
Qy 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SVPDPQPIGEPPAAPSGVGSLTMASGGGAPVADNNEGADGVGSSSGNWHCDSQWLGDRVI 240
Qy 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TTSTRTWALPTYNNHLYKQISNSTSGGSSNDNAYFGYSTPWGYFDFNRFHCHFSPRDWQR 300
Qy 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 LINNNWGFRPKRLNFKLFNIQVKEVTDNNGVKTIANNLTSTVQVFTDSDYQLPYVLGSAH 360
Qy 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EGCLPPFPADVFMIPQYGYLTLNDGSQAVGRSSFYCLEYFPSQMLRTGNNFQFSYEFENV 420
Qy 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PFHSSYAHSQSLDRLMNPLIDQYLYYLSKTINGSGQNQQTLKFSVAGPSNMAVQGRNYIP 480
Qy 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 GPSYRQQRVSTTVTQNNNSEFAWPGASSWALNGRNSLMNPGPAMASHKEGEDRFFPLSGS 540
Qy 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LIFGKQGTGRDNVDADKVMITNEEEIKTTNPVATESYGQVATNHQSAQAQAQTGWVQNQG 600
Qy 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 ILPGMVWQDRDVYLQGPIWAKIPHTDGNFHPSPLMGGFGMKHPPPQILIKNTPVPADPPT 660
Qy 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720 ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 AFNKDKLNSFITQYSTGQVSVEIEWELQKENSKRWNPEIQYTSNYYKSNNVEFAVNTEGV 720
Qy 721 YSEPRPIGTRYLTRNL 736
||||||||||||||||
Db 721 YSEPRPIGTRYLTRNL 736
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 use known AAV9 VP1 as disclosed by Kay in the viral particle disclosed in Sun/Tian and Banfi, 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 skill in the art would have been expected to have a reasonable expectation of success because prior art teaches the relevant sequence of AAV9 VP1. 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
To the extent that Applicants’ arguments are pertinent to the modified new rejections, they are addressed as follows:
Applicant disagree with the rejection arguing Sun as the starting point for assessing inventiveness, Sun does not teach use of the hRPE65 polynucleotide sequence of SEQ ID NO: 2 as set forth in claim 1 of the present invention. Applicant further submits that a skilled artisan in view of Sun would fail to have a reason or necessary motivation to use the RPE65 coding sequence of amended claim 1, which Applicant notes is a wild-type sequence. This is because paragraph [0076] of Sun teaches that the inventor made special optimization of RPE65 coding sequence the expression amount of the specially optimized RPE65 coding sequence (SEQ ID NO: 1) was significantly improved compared to un-optimized coding sequence and was very suitable for expression in mammalian (especially human) cells to effectively treat Leber. On this basis, the inventor completed the present invention By teaching that optimization of the RPE65 coding sequence allegedly improves its expression relative a un-optimized coding sequence, Sun explicitly teaches away from using the wild-type RPE65 coding sequence (SEQ ID NO: 2) of the present invention, let alone its operable linkage to the CAG promoter and other elements as set forth the in claim 1. Applicants’ arguments have been fully considered, but are not found persuasive.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Applicants have further engaged in selective reading of the teachings of Sun and Tian to formulate the grounds for teaching away. It should be noted that the ultimate goal of delivering hRPE55 to the ocular tissue is to treat the retinal dystrophy. As previously indicated, Sun teaches a rAAV particle comprising an AAV9 serotype comprising cap gene and a vector comprising a left ITR sequence; a ubiquitous CAG promoter, a nucleic acid encoding a hRPE65 polypeptide a human growth hormone (hGH polyA); and a right ITR sequence (see para. 42-47). While Sun teaches a codon optimized RPE65 coding sequence, however, prior art taches a variety of suitable coding sequence for this purpose are well-known in the art, including the wild type human PRE65. Banfi cure the deficiency by disclosing use of recombinant expression vector comprising one or more wild-type form of a coding sequence responsible for the retinal dystrophy under the control of a suitable promoter or use in the treatment and/or prevention of a retinal dystrophy, wherein one or more coding sequence include SEQ ID NO: 37 that has 100% sequence identity to SEQ ID NO: 2 of instant application. To the extent that Banfi describe the use of wild type coding sequence of SEQ ID NO: 37 encoding hRPE65 for treatment of retinal dystrophy, the rejection is applicable to the instant case. Applicants' selective reading of Sun/Tian ignores the teachings of Banfi. There is no requirement for Sun/Tian to teach that which is clearly taught by Banfi. A person of skill in the art would be motivated to combine the teachings of prior art to modify the AAV comprising a vector genome encoding human RPE65 as disclosed in Sun/Tian with structurally and functionally equivalent wild type human RPE65 coding sequence as disclosed in Banfi, as instantly claimed, with a reasonable expectation of success, because the method would allow treating or preventing retinal dystrophy, with a reasonable expectation of success.
Applicant continue to argue that non-obviousness of the AAV vector configuration of the present invention is further evidenced by its unexpected and superior technical effects. Specifically, as described in working Example 1 of the present application (see page 17, lines 41-50 of the PCT publication of the present application), None of the cited references, alone or in combination, teach or suggest that the rescue of visual function by AAV-delivered RPE65 gene replacement therapy can be improved by using AAV9 delivery instead of AAV2 delivery. Applicants’ arguments have been fully considered, but are not found persuasive.
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., rescue of visual function by using AAV9 delivery) are not recited in the rejected claim(s). 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). Further, any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Sun teaches a rAAV particle comprising an AAV9 serotype comprising cap gene and a vector comprising a left ITR sequence; a ubiquitous CAG promoter, a nucleic acid encoding a hRPE65 polypeptide a human growth hormone (hGH polyA); and a right ITR sequence (see para. 42-47). Thus, the relevance of Applicants' arguments with respect to non-obviousness of the AAV vector configuration is not apparent. Further, use of wild type coding sequence of hRPE65 are described by Banfi. Such use of wild type coding sequence and codon optimized sequence of gene of interest was considered routine in the prior art. Therefore, the fact that prior art of Banfi describe the use of wild type coding sequence of SEQ ID NO: 37 encoding hRPE65 for treatment of retinal dystrophy is an expected result, and is the goal behind use of wild type coding sequence of RPE65 as set forth in SEQ ID NO: 3. As indicated in MPEP 716.02(c), Where the unexpected properties of a claimed invention are not shown to have a significance equal to or greater than the expected properties, the evidence of unexpected properties may not be sufficient to rebut the evidence of obviousness. In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977). “Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof.” In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Applicant’s argument of improved expression by using AAV9 delivery instead of AAV2 delivery is not persuasive because prior art explicitly reported using AAV9 delivery. Applicant fail to provide any evidence showing expression level observed after delivery of wild type hRPE65 is significantly better than delivery of codon optimized hRPE65 sequence using the sameAAV9 vector configuration. Further, unexpected results have to be commensurate with the scope of the invention. "Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980)." Example 1 discloses rAAV9 vector (AAV9-CAG-hRPE65, "HG004") with an AAV9 serotype capsid encapsidating therein a vector genome of SEQ ID NO: 1. The rejected claims are not so limited.
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.
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 ANOOP K. SINGH whose telephone number is (571)272-3306. The examiner can normally be reached Monday-Friday, 8AM-5PM. 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, Peter Paras can be reached at (571)272-4517. 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.
/ANOOP K SINGH/ Primary Examiner, Art Unit 1632
Prosecution Insights