Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
In light of Applicant’s arguments and the amended claims 57 and 58, present application is being examined under the pre-AIA first to invent provisions.
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 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.
Amendments
In the reply filed 8/04/2026, Applicant has amended Claim 57.
Claims 62-73 are pending but withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 56-61 are under consideration.
Withdrawn 35 USC § 112(a)
New Matter
The prior rejection of Claims 57-58 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments of Claim 57 to no longer recite that the nucleic acid is a mRNA.
Written Description
The prior rejection of Claims 57-58 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of Applicant’s amendments of Claim 57 to no longer recite that the nucleic acid is a mRNA.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) 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.
Claims 56, 60, and 61 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lawlor et al., (WO2010/071454, filed 12/17/2009, published 6/24/2010, see IDS filed 7/06/2023), in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023).
Lawlor teaches a recombinant AAV vector for comprising
a nucleic acid comprising a promoter operably linked with an aspartoacylase (ASPA) sequence (p. 4, last para., p. 5, 4th para., pgs.23-24, Example 13, see also Claims 1-8 of Lawlor), and
a capsid protein having the amino acid sequence of an AAV9 (p. 5, 2nd para., p. 11, 2nd - 3rd para. see Fig. 8).
However, Lawlor is silent with respect to the amino acid sequence for the capsid of AAV9. Nevertheless, Lawlor cites the prior art of Gao et al. (2004) (see reference #30 of Lawlor).
Gao et al. (2004) teaches the amino acid sequence for the capsid of AAV9. Importantly, the amino acid sequence taught by Gao is 100% identical to the SEQ ID NO: 8 (SCORE Search Result 20260419, rup.file, Result #1)
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to prepare the rAAV9-ASPA vector as taught by Lawlor, and choose a nucleic acid that encodes the amino acid sequence of the AAV9 capsid as taught by Gao with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so for several reasons. First, since Lawlor cites Gao for the making of the AAV9 vector, therefore it would have been obvious to the ordinary artisan to turn to the cited art for an enabling disclosure of the AAV9 sequence. Furthermore, the successful cloning and sequencing of a DNA encoding a known protein is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009). In instant case, Lawlor provides the motivation to make and use a sequence for the production of the AAV9 capsid, while Gao provides the reasonable expectation of success for doing so by describing the sequence.
In regard to claim 60, Lawlor teaches the promoter is a tissue specific promoter (p. 4, last para., p. 14, 2nd para.).
In regard to claim 61, Lawlor teaches the rAAV is delivered by infusion into a subject (p. 1, Background, 2nd para., p.11, Fig. 8, legend), which makes obvious to include a pharmaceutically acceptable carrier.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 8/04/2026 are acknowledged.
Applicant argues that one of ordinary skill in the art would not have been motivated to choose the combination of the AAV9 capsid of SEQ ID NO:8 with an ASPA transgene according to the teachings of Lawlor and Gao. Specifically, Applicant argues that Lawlor teaches that several types of transgenes can be delivered by several types of AAV. Applicant argues that the Examiner has not supplied rational for specifically choosing and AAV9 with ASPA.
Furthermore, Applicant argues that Lawlor demonstrates AAV8 capsid vectors can efficiently transduce oligodendrocytes. By contrast, Applicant argues that Figs. 5 & 7 vs Fig.8 of Lawlor indicates that AAV9 mostly transduce astrocytes. Applicant argues that although Lawlor teaches the ability to transduce oligodendrocytes for the expression of ASPA will be useful in developing treatments for Canavan disease, the AAV targeting of neurons has limited these developments, and that AAV1/2 capsid with a CAG promoter expressing ASPA did not improve Canavan disease in a rat model. Based on the fact that is ASPA was known to be expressed in oligodendrocytes, one of ordinary skill would not have chosen AA9 capsid with a reasonable expectation of success.
Applicant's arguments have been fully considered but they are not persuasive.
In regard to Applicant’s first arguments, as acknowledged by Applicant, Lawlor teaches “The ability to efficiently transduce oligodendrocytes…will be useful in developing treatments for leukodystrophies such as Canavan disease” and goes on to explain “this have been limited by the fact that AAV preferentially targets neurons e.g., AAV-mediated neuronal overexpression of ASPA did not improve pathology or behavioral deficits in a rat model of Canavan disease” (p. 15, 2nd para. of Lawlor). Thus, Lawlor is clearly directed to AAV gene therapy of Canavan disease by expressing ASPA. Furthermore, Lawlor explains the problem is the widespread tropism of AAV vectors, and provides a solution for rectifying this problem with tissue specific promoters. Specifically, Lawlor states “According to a first aspect, the present invention provides a purified adeno-associated viral (AAV) vector stock comprising a vector having a cell specific promoter“ (p. 4, Summary of the Invention, see also Claim 1 of Lawlor). Thus, Lawlor provides strong motivation to make and use an AAV-ASPA vector.
In regard to choosing AAV9, Lawlor clearly teaches using AAV9 (see p. 5, 2nd para., “A vector such as AAV9 may also be used in the methods of the present invention”) and provides working examples of an AAV9 with a generic non-cell specific CBA promoter as well as with an astrocyte specific GFAP promoter (p. 11, 2nd - 3rd para., see Fig. 8). Although Lawlor does not reduce to practice an AAV9 with an oligodendrocyte specific promoter, as acknowledged by Applicant, Lawlor is clear that in order for an AAV-ASPA to successfully treat Canavan disease, an oligodendrocyte promoter must be used and discloses several of these that could be used (e.g., MBP or ASPA promoters). Thus, even though Lawlor does not provide a preferred embodiment of an AAV9-ASPA with an oligodendrocyte promoter, the MPEP 2123 (I) states that patents are relevant as prior art for all they contain, and that a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. In instant case, the AAV9 vectors, the ASPA transgene, oligodendrocyte specific promoters are typical agents found in the gene therapy art and appear both in the specification and in the claims of Lawlor. Applicant is reminded that preferred embodiments are not the only teaching of a reference. “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) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Furthermore, in regard to Applicant arguments Fig.8 of Lawlor indicates that AAV9 mostly transduced astrocytes, as stated supra, these experiments were conduced with an AAV9-GFAP promoter. Thus, contrary to Applicant’s assertion, Lawlor indicates that AAV9 based expression of a transgene is dependent on the type of tissue specific promoter used. In other words, AAV9-CBA promoter expressed in all neurons, AAV9-GFAP promoter expressed in astrocytes, and it would have been expected that AAV9-MBP promoter or AAV9-ASPA promoter would have expressed in oligodendrocytes. Furthermore, it must be noted that instant claims do not recite an “oligodendrocyte specific promoter”. 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). The court explained that “reading a claim in light of the specification, to thereby interpret limitations explicitly recited in the claim, is a quite different thing from ‘reading limitations of the specification into a claim,’ to thereby narrow the scope of the claim by implicitly adding disclosed limitations which have no express basis in the claim.” The court found that applicant was advocating the latter, i.e., the impermissible importation of subject matter from the specification into the claim.). See also In re Morris, 127 F.3d 1048, 1054-55, 44 USPQ2d 1023, 1027-28 (Fed. Cir. 1997) (The court held that the PTO is not required, in the course of prosecution, to interpret claims in applications in the same manner as a court would interpret claims in an infringement suit. Rather, the “PTO applies to verbiage of the proposed claims the broadest reasonable meaning of the words in their ordinary usage as they would be understood by one of ordinary skill in the art, taking into account whatever enlightenment by way of definitions or otherwise that may be afforded by the written description contained in applicant’s specification.”). See MPEP 2111]
Claims 57-58 are rejected under 35 U.S.C. 103(a) as being unpatentable over Lawlor et al., (WO2010/071454, filed 12/17/2009, published 6/24/2010, see IDS filed 7/06/2023), in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023), as applied to claim 56, in further view of Naldini et al. (WO2007/000668, filed 5/26/2006, published 1/04/2007, see IDS filed 7/06/2023)
As discussed previously, Lawlor and Gao suggest and rAAV9-ASPA vector comprising the capsid of SEQ ID NO:8.
However, although Lawlor teaches that transduction of organs outside the CNS is undesirable (p. 4, 1st para.), they are silent with respect to combining one or more microRNA binding sites for microRNA that are more abundant in non-CNS tissue than CNS tissue.
In regard to Claim 57, Naldini teaches and claims how engineered viral vectors comprising one or more microRNA binding sites can be down-regulated by endogenous microRNAs for controlling transgene expression to achieve specific expression profiles of a vector (p. 2, last para. to p. 4, 1st para., p. 7, 4th para., see also Claims 1-5 and 18 of Naldini). Specifically, Naldini teaches the viral vector can be an AAV (p. 5, lines 14-15, p. 52, line 4-5). Furthermore, and in regard to claim 58, Naldini teaches level of suppression of transgene in a particular tissue corresponds to the abundance of the microRNA in that tissue (p.7, last two para. to p. 8, 2nd para.), and Naldini teaches one or more microRNA that are at least two-fold higher in non-CNS tissue (p. 21, 1st para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to prepare the rAAV9-ASPA vector for the transduction of the CNS as suggested by Lawlor and Gao, and combine one or more microRNA binding sites for microRNA that are more abundant in non-CNS tissue than CNS tissue as taught by Naldini with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Naldini because miRNA-regulation can be used to effectively de-target transgene expression from a particular cell type (i.e., non-CNS tissue), and Naldini goes on to explain that miRNA regulation may also be used as a complimentary approach to regulating a transgene by a promoter. By including the miRNA target sequence in expression cassettes already under the control of a tissue-specific promoter, one adds an additional layer of regulation which will eliminate off-target expression (p. 9, 2nd para.).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 8/04/2026 are acknowledged and have been addressed supra.
Claim 59 is rejected under 35 U.S.C. 103(a) as being unpatentable over Lawlor et al., (WO2010/071454, filed 12/17/2009, published 6/24/2010, see IDS filed 7/06/2023), in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023), as applied to claim 56, in further view of Wang et al., (Gene Therapy, 2003, 10:2105-2111, prior art of record)
As discussed previously, Lawlor and Gao suggest and rAAV9-ASPA vector comprising the capsid of SEQ ID NO:8.
However, Lawlor and Gao are silent with respect to the rAAV vector being a self-complementary (sc)AAV.
Wang teaches an rAAV comprising a promoter operably linked to a transgene, wherein the rAAV is a scAAV (Abstract, p. 2109, Materials and Methods, last para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time invention was made to prepare the rAAV9-ASPA as suggested by Lawlor et al. and substitute the rAAV for an scAAV as taught by Wang with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Wang because the scAAV vector exhibits superior and accelerated transduction compared to the single-stranded rAAV vector (Abstract).
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 8/04/2026 are acknowledged and have been addressed supra.
Terminal Disclaimer
The terminal disclaimer filed on 8/04/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12,491,235 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawn Double Patenting
The prior rejection of Claims 56, 60, and 61 on the grounds of nonstatutory double patenting over claims 1-15, and 17-18 of U.S. Patent No. 12,491,235 (Gao et al., Patented 12/09/2025) in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023) is withdrawn in light of the terminal disclaimer
The prior rejection of Claim 59 on the grounds of nonstatutory double patenting over claims 1-15, and 17-18 of U.S. Patent No. 12,491,235 (Gao et al., Patented 12/09/2025) in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023), in further view of Wang et al., (Gene Therapy, 2003, 10:2105-2111) is withdrawn in light of the terminal disclaimer
Provisional Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
Claims 56, 59-61 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/857,527, in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the rAAV9 composition comprising a promoter operably linked to an ASPA sequence of cited application makes obvious the composition of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the instant application claims are more specific to the AAV9 capsid sequence.
Gao et al. (2004) teaches the amino acid sequence for the capsid of AAV9. Importantly, the amino acid sequence taught by Gao is 100% identical to the SEQ ID NO: 8 (SCORE Search Result 20260419, rup.file, Result #1)
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to prepare the rAAV9-ASPA vector as claimed by cited application, and claim a nucleic acid that encodes the amino acid sequence of the AAV9 capsid as taught by Gao with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so because the successful cloning and sequencing of a DNA encoding a known amino acid sequence is obvious, and thus unpatentable, if (1) there was some suggestion or motivation in the prior art to clone the cDNA, and (2) there was a “reasonable expectation of success,” based on "detailed enabling methodology" in the prior art. Ex parte Kubin, 83 U.S.P.Q.2d (BNA) 1410 (B.P.A.I. 2007), aff'd, 561 F.3d 1351 (Fed. Cir. 2009).
Since the instant application claims are obvious over cited application claims in view of Gao, said claims are not patentably distinct.
Claims 57-58 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/857,527, in view of Gao et al., (J Virol, 2004, 6381-6388, see IDS filed 7/06/2023) as applied to claim 56, in further view of Naldini et al. (WO2007/000668, filed 5/26/2006, published 1/04/2007, see IDS filed 7/06/2023). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented
The subject matter claimed in the instant application is disclosed in the referenced application as follows: the rAAV9 composition comprising a promoter operably linked to an ASPA sequence of cited application makes obvious the composition of instant application. It is clear that elements of the cited application claims are to be found in instant claims. The difference between the cited application claims and the instant claims lies in the fact that the instant application claims are more specific to the nucleic acid comprising one or more microRNA binding sites.
In regard to Claim 57, Naldini teaches and claims how engineered viral vectors comprising one or more microRNA binding sites can be down-regulated by endogenous microRNAs for controlling transgene expression to achieve specific expression profiles of a vector (p. 2, last para. to p. 4, 1st para., p. 7, 4th para., see also Claims 1-5 and 18 of Naldini). Specifically, Naldini teaches the viral vector can be an AAV (p. 5, lines 14-15, p. 52, line 4-5). Furthermore, and in regard to claim 58, Naldini teaches level of suppression of transgene in a particular tissue corresponds to the abundance of the microRNA in that tissue (p.7, last two para. to p. 8, 2nd para.), and Naldini teaches one or more microRNA that are at least two-fold higher in non-CNS tissue (p. 21, 1st para.).
Accordingly, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was claimed to prepare the rAAV9-ASPA vector for the transduction of the CNS as claimed by cited application, and combine one or more microRNA binding sites for microRNA that are more abundant in non-CNS tissue than CNS tissue as taught by Naldini with a reasonable expectation of success. The ordinary skilled artisan would have been motivated to do so as taught by Naldini because miRNA-regulation can be used to effectively de-target transgene expression from a particular cell type (i.e., non-CNS tissue), and Naldini goes on to explain that miRNA regulation may also be used as a complimentary approach to regulating a transgene by a promoter. By including the miRNA target sequence in expression cassettes already under the control of a tissue-specific promoter, one adds an additional layer of regulation which will eliminate off-target expression (p. 9, 2nd para.).
Since the instant application claims are obvious over cited application claims in view of Gao and Naldini, said claims are not patentably distinct.
RESPONSE TO ARGUMENTS
Applicant's arguments filed on 8/04/2026 are acknowledged.
Applicant argues that since the claims are in condition for allowance, and cited application has a later filing date, the provisional rejection should be withdrawn.
Applicant’s arguments have been fully considered but not found persuasive because the examined claims are not in condition for allowance.
Conclusion
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 extension fee 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 date of this final action.
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARTHUR S LEONARD whose telephone number is (571)270-3073. The examiner can normally be reached on Mon-Fri 9am-5pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James Doug Schultz can be reached on 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ARTHUR S LEONARD/Examiner, Art Unit 1631
