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 .
Election/Restrictions
Claims 1-14 and 32-35 are pending.
Applicant's election with traverse of Group I, and the species of a method of treating a patient having FRDA in the reply filed on 02/17/2026 is acknowledged. However, because Applicant did not identify specific flaws in the restriction requirement, the requirement is still deemed proper and is therefore made FINAL.
Claims 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 02/17/2026.
Claims 1-9, 14, and 32-35 have been examined on their merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. See Table, p73, reference to Jackson Laboratories.
Claim Objections
Claim 1 is objected to for the following informalities: claim 1 recites “FRDA.” Abbreviated terms should be spelled out in their first instance. “Friedreich’s Ataxia (FRDA)” would be ameliorative.
Claim Rejections - 35 USC § 112(b)
Claims 32-35 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 32 and 33 recite the phrase “intraparenchymal (dentate nucleus).” This is indefinite because it is unclear whether the limitations within the parentheses are part of the claimed invention or are exemplary (see MPEP § 2173.05(d)). For compact prosecution, the parenthetical limitation (i.e., “dentate nucleus”) have been interpreted as optional.
Claims 33-35 are also rejected under 35 USC 112(b) for their dependency on claim 32.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024) as evidenced by Buck et al. (International Journal of Molecular Science, 2020).
In regards to claim 1, Samulski teaches methods for treating patients with Friedrich’s Ataxia (FRDA) (claim 16). Samulski teaches that an embodiment of the invention is to avoid neutralizing antibodies in these patients (paragraph [0138]). Continuing, Samulski teaches that the method comprises administering a rAAV having a capsid and a vector genome comprising a FXN gene (claims 1, 7, and 9).
While the FXN gene sequence as taught by Samulski (SEQ ID NO: 3) does not have at least 95% identity with the claimed SEQ ID NO: 3 (which appears to have about 90% identity, see International Search Report on 01/11/2021), sequences with at least 95% identity with the claimed SEQ ID NO: 3 were known in the art before the effective filing date.
Specifically, Corti teaches FXN gene sequence (SEQ ID NO: 2) that has 97.2% identity with the claimed SEQ ID NO 3 (see Search Results on 03/05/2026, 20260304_155654_us-18-260-786a-3.rnpbm, Pending_Patents_NA_Main; Result no. 6).
Applicant should note that that the successful cloning and sequencing of the cDNA 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 the instant case, a person of ordinary skill in the art would have been motivated to utilize the FXN gene sequence as disclosed by Corti because Corti teaches that the specific sequence is useful for use for treating a patient with Friedrich’s Ataxia (FRDA) comprising administering a rAAV having a capsid and a vector genome (polynucleotide) comprising a FXN gene (claims 1 and 28; paragraph [0079]).
Furthermore, because Corti teaches that the FXN nucleic acids can be provided as cDNA (paragraph [0047]) and because Samulski and Corti are in the same technical field of treating FRDA with rAAV vectors comprising a FXN gene, it could have been done with predictable results and a reasonable expectation of success.
While Samulski teaches that the method comprises administering empty capsids in order to avoid neutralizing antibodies (paragraph [0138]), Samulski does not explicitly teach a step of administering a ligand which inhibits binding of a human neonatal Fc receptor (FcRn) and immunoglobulin G (IgG) (it is noted that this has been interpreted as meaning binding a FcRN to IgG).
However, methods for administering ligands which inhibit binding of an FcRn and IgG was known in art before the effective filing date.
Specifically, Mezo teaches that administering peptides (ligands) that block the binding of FcRn and IgG are useful for treating inflammatory diseases (Abstract; paragraphs [0009, 0046]; clam 117).
In regards to FRDA specifically, as taught by Delatycki, inflammation is important to the pathogenesis of FRDA and recommends therapies including modulators of inflammation (Abstract, p2; Inflammation in FRDA, p4).
Therefore, a person of ordinary skill in the art would have been motivated to include a step of administering ligands which inhibit binding of an FcRn and IgG in order to address the inflammation associated with the pathogenesis of FRDA. Furthermore, because Delatycki recommends therapies that modulate inflammation, and because Mezo teaches specific methods for administering peptides (ligands) that block the binding of FcRn and IgG for treating inflammatory diseases, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 2, SEQ ID NO: 2, as taught by Corti results in a protein having a sequence that is 100% to the claimed SEQ ID NO: 2.
In regards to claim 3, Samulski teaches that the rAAV vector can comprise a 5’ and 3’ ITRs, introns, the FXN gene, and a poly A (claims 1, 7, and 9; paragraphs [0042 and 0089-0091]).
In regards to promoters, Samulski teaches that the promoter can be a CBA promoter or a CBh, which is a promoter derived from the chicken-actin (CBA) gene and cytomegalovirus (CMV) enhancer (paragraphs [0089-0090]). As evidenced by Buck, CB7 is a shortened CMV early enhancer element and a chicken β-actin promoter (p8, second paragraph) and appears to be the same as CBA (“CBA aka CB7”) (p10, Ubiquitous Promoters in rAAV-Vectors) or at least is an art recognized equivalent for the same purpose (see MPEP 2144.06).
In regards to claim 32, Samulski teaches that administration may be intravenous (paragraph [0139]).
Therefore, the combined teachings of Samulski, Corti, Mezo, and Delatycki renders the invention unpatentable as claimed.
Claims 4-5 are rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024), as applied to claim 1 above, and further in view of Hordeaux et al. (US20210077553A1, priority to 10/23/2019).
In regards to claims 4-5, Corti teaches that FRDA is associated with pathological conditions in the dorsal root ganglia (DRG) (paragraph [0035]).
Corti also teaches that rAAV vectors for treating patients with FRDA (claims 1 and 28; paragraph [0079]) can comprise sequences which facilitate expression of a transgene including silencers (paragraph [0074], miRNAs are a known type of silencer), but is silent about miRNAs specifically.
However, as taught by Hordeaux, delivering AAV vectors to the central nervous system of subjects is associated with DRG toxicity, but that introduced miRNA sequences reduces toxicity (paragraphs [0003-0008]; claims 17 and 29). Hordeaux teaches that the sequences can comprise at least two tandem repeats which may be the same (paragraph [0009-0008]).
Therefore, a person of ordinary skill in the art would have been motivated to include DRG-specific miRNA sequences in a vector genome targeting sequence in order to minimize toxicity in the region of the brain that is being treated.
Furthermore, because Hordeaux teaches that DRG-specific miRNAs can be introduced with AAVs (claims 17 and 29) and because Corti teaches that AAV vectors can comprise sequences which facilitate expression of a transgene including silencers (of which miRNAs are a type), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Samulski, Corti, Mezo, Delatycki, and Hordeaux renders the invention unpatentable as claimed.
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024), as applied to claim 1 above, and further in view Nambiar et al. (US20220249705A1, priority to 04/28/2020).
In regards to claims 6, Samulski teaches various AAVrh capsids (claim 9) and broadly teaches that the capsid may be “any other AAV now known or later discovered” (paragraph [0101]), but does not teach an AAVrh91 capsid specifically.
However, Nambiar teaches rAAV capsids, including specifically, an AAVrh91 capsid (AAVrh.91.93) (paragraphs [0004]). A person of ordinary skill in the art would have been motivated to use this rAAV capsid because Nambiar teaches that this capsid has reduced immunogenicity, increased storage stability, and increased transduction of a selected target tissue pampered to prior art AAVs (Abstract; paragraph [0050]).
Furthermore, because Nambiar teaches an AAVrh91 capsid, which can be used to tissues including brain and lung (paragraph [0053]) (well-known sites of FRDA pathology), and because Samulski broadly teaches that any capsid can be used, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Samulski, Corti, Mezo, Delatycki, and Nambiar renders the invention unpatentable as claimed.
Claims 7-9 are rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024), as applied to claim 1 above, and further in view of and Guclu et al. (J Med Cases, 2014) and Limberis et al. (US20180243416A1).
In regards to claims 7-8, as above, Samulski broadly teaches that the capsid may be “any other AAV now known or later discovered” (paragraph [0101]), but does not teach a AAVhu68 clade F capsid specifically.
It is well-known in the art that FRDA, in addition to targeting the brain (DRG specifically) also results in lung pathology. Indeed, as taught by Guclu, FRDA causes comorbidities such as restrictive lung disease (Introduction, p232).
In regards to rAAV capsids, Limberis teaches rAAV capsids, including specifically, a clade F AAVhu68 capsid (claim 17; paragraph [0037). A person of ordinary skill in the art would have been motivated to select a clade F AAVhu68 capsid because Limberis teaches that the vector has strong expression in the lung (paragraph [0018]) and therefore, this vector would be efficient for alleviating FRDA lung comorbidities such as restrictive lung disease.
Furthermore, because Limberis teaches a clade F AAVhu68 capsid, and because Samulski broadly teaches that any capsid can be used, it could have been done with predictable results and a reasonable expectation of success.
In regards to claim 9, Limberis teaches a AAVhu68 vp1 (SEQ ID NO: 18; see Result 1, 20260304_155654_us-18-260-786a-4.rnpbm), with 100% identity to the proteins produced from SEQ ID NO: 4.
As above, Applicant should note that that the successful cloning and sequencing of the cDNA 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 the instant case, a person of ordinary skill in the art would have been motivated to use sequence that encodes vp1 proteins from SEQ ID NO: 18 as taught by Limberis because teaches that these vectors are useful to provide a therapeutic benefit without undue adverse effects, or with medically acceptable physiological effects (paragraph [0181]).
Furthermore, because Limberis teaches that it is within the skill in the art to design nucleic acid sequences encoding a AAVhu68 capsid, including DNA (genomic or cDNA), or RNA (e.g., mRNA), and specially as provided SEQ ID NO: 18 (paragraph [0121]), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Samulski, Corti, Mezo, Delatycki, Guclu, and Limberis renders the invention unpatentable as claimed.
Claim 14 is rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024), as applied to claim 1 above, and further in view Spiegel et al. (WO2021072269, priority to 10/09/2020).
In regards to claim 14, in regards to a specific ligand that inhibits binding of FcRn and IgG, a person of ordinary skill in the art would have been motivated to select rozanolixizumab because Spiegel teaches that rozanolixizumab is suitable known FcRn antagonist (p138, claim 3) to promote or enhance degradation of circulating proteins such as IgG specifically (Abstract; Background of the Disclosure, p1). Furthermore, because rozanolixizumab is a known suitable FcRn antagonist, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Samulski, Corti, Mezo, Delatycki, and Spiegel renders the invention unpatentable as claimed.
Claims 33-35 are rejected under 35 U.S.C. 103 as being unpatentable over Samulski (US20170128528A1, on IDs 01/27/2024) in view of Corti et al. (US20240058477A1, priority to 01/04/2021), Mezo et al. (US20110059889A1, on IDS 01/27/2024), and Delatycki et al. (Neurobiology and Disease, 2019, on IDS 01/27/2024), as applied to claim 1 above, and further in view Sah et al. (US2016059302).
In regards to claims 33-35, as above, Samulski teaches that administration may be intravenous (paragraph [0139]). Additionally, Samulski teaches that administration may be done directly into tissues (paragraph [0139]) and identifies the dentate nucleus as a tissue containing frataxin (paragraph [0190-0192]), and therefore, intraparenchymal administration (into the brain parenchyma) would have been an obvious embodiment.
Specifically, a person of ordinary skill in the art would have been motivated to administer intraparenchymally in order to treat FRDA at the specific cites of frataxin dysregulation. Furthermore, Sah teaches AAV vectors can be administered to at least one site (unilaterally) or bilaterally (claim 10; paragraph [00282]) and as above, Samulski teaches that administration can be done directly into tissues, it could have been done with predictable results and a reasonable expectation of success.
In regards to the timing of sequentially administering the rAAV within a 24hr period, Sah teaches that AAV particles can be co-administered with lapses of less than 24 hours (paragraph [00010]). A person of ordinary skill in the art would have been motivated to sequentially administer rAVV vectors in order to reduce patient stress.
Additionally, Applicant should note that according to MPEP 2144(IV)(C), the selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Burhans, 154 F.2d 690, 69 USPQ 330 (CCPA 1946); see also In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930) (Selection of any order of mixing ingredients is prima facie obvious).
Therefore, the combined teachings of Samulski, Corti, Mezo, Delatycki, and Sah renders the invention unpatentable as claimed.
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 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-9, 14, and 32-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 10-18, 26, 46, and 50-53 of copending Application No. 17/787,013 in view of Limberis et al. (US20180243416A1).
While this is a provisional nonstatutory double patenting rejection, it is noted that a notice of allowance for Application No. 17/787,013 was mailed on 12/05/2025, but that the application has not yet published as a patent. When Application No. 17/787,013 publishes as a patent, this rejection will convert to a nonstatutory double patenting rejection.
While the instant claims and claims 1, 3-8, 10-18, 26, 46, and 50-53 of copending Application No. 17/787,013 are not identical, they are not patentable distinct because the claims of both applications are drawn to methods for treating FRDA in a subject with a rAAV comprising an AAV capsid and a FXN gene targeted to human cells wherein the FXN gene comprises sequences with 100% identity SEQ ID NO: 3, claims 52 and 53) that encodes a frataxin protein that is 100% identical to the instant SEQ ID: NO 2.
In regards to instant claim 9, while of copending Application No. 17/787,013 discloses that the vector can comprise a AAVhu68 capsid (claims 7-8), copending Application No. 17/787,013 is silent as to the sequence of the vp1 proteins.
However, as above, Limberis teaches a AAVhu68 vp1 (SEQ ID NO: 18; see Result 1, 20260304_155654_us-18-260-786a-4.rnpbm), with 100% identity to the proteins produced from SEQ ID NO: 4.
As above, Applicant should note that that the successful cloning and sequencing of the cDNA 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 the instant case, a person of ordinary skill in the art would have been motivated to use sequence that encodes vp1 proteins from SEQ ID NO: 18 as taught by Limberis because teaches that these vectors are useful to provide a therapeutic benefit without undue adverse effects, or with medically acceptable physiological effects (paragraph [0181]).
Furthermore, because Limberis teaches that it is within the skill in the art to design nucleic acid sequences encoding a AAVhu68 capsid, including DNA (genomic or cDNA), or RNA (e.g., mRNA), and specially as provided SEQ ID NO: 18 (paragraph [0121]), it could have been done with predictable results and a reasonable expectation of success.
Conclusion
No claims are allowed.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631