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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.
Applicant’s submission filed 4/10/2026 has been entered and fully considered. In that response, applicant submitted amendments to the claims and arguments traversing the outstanding rejections. Claims 41-58 are currently pending for examination, with claims 59-60 canceled. Claims 41-58 are currently pending for examination, and claims 59-60 are canceled.
The present Office action addresses the amended claims and applicant’s arguments in response to the prior Office action.
Claim Rejections - 35 USC § 103 – Maintained
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.
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 41-54, 56, and 57 are rejected under 35 U.S.C. 103 as being unpatentable over Pyle et al. (WO 2017/139505 A2; 17 August 2017), in view of Gersbach et al. (WO 2014/197748 A1; 11 December 2014), Chew et al. (A multifunctional AAV-CRISPR-Cas9 and its host response, Nat Methods 13, 868-874 (2016)), Byrne et al. (WO 2015/164758 A1; 29 October 2015), and Cramer et al. (Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone, Hum Gene Ther. 2017 Jun;28(6):493-509).
The following rejection has been slightly redrafted from the previous version to better coincide with the response to Applicant’s arguments.
Regarding Claims 41-51, 53 and 54, applicant references WO 2017/139505 (“Pyle et al.”) as disclosing a CRISPR/Cas9 system targeting Duchenne muscular dystrophy (see Specification pg. 2). Pyle et al., presumably previous work from applicant, appears to disclose and claim nearly all elements of the instantly claimed invention absent use of AAV gene therapy vectors and immunosuppressive agents (see Pyle et al., Claims 37-54, Example 1 [00273]-[00290], treating Duchenne muscular dystrophy (DMD), CRISPR/Cas9 gRNAs, Cpf1, SEQ ID NO: 1134 & 1162, deletion sizes ∼330kb & ∼700kb). Pyle thus teaches the DMD/BMD gene-editing framework recited in the instant claims, including the relevant dystrophin-targeting strategy and deletion endpoints.
AAV Gene Therapy Vectors
Pyle et al. does not expressly teach use of AAV gene therapy vectors. Gersbach et al. teaches use of AAV vectors comprising CRISPR/Cas9 constructs for treatment of DMD (see [00188]). Gersbach et al. notes that AAV is not pathogenic and causes a mild immune response (see [00113]).
Regarding Claims 56 and 57, Gersbach et al. teaches multiple vectors (see [00188]) and muscle-specific promoters (see [00208]).
It would have been prima facie obvious to a skilled artisan at the time of filing to utilize AAV vectors as discussed in Gersbach et al. within the methods of Pyle et al. due to the recognized advantages of such vectors within CRISPR-Cas gene therapy systems, particularly for muscle-directed therapy. A skilled artisan would have expected successful implementation of such elements because Gersbach et al. suggest use of such vectors within CRISPR-Cas gene therapy systems similar to those of Pyle et al., and because both references address DMD-related gene editing.
Use of Immunosuppressants
Pyle et al. does not teach use of immunosuppressants.
Chew et al. describes development of an AAV CRISPR/Cas9 gene therapy system and monitoring of the host immune response (see pg. 2, Introduction). Chew et al. recognized that while AAV vectors are advantageous for gene therapy, they may cause a detrimental host immune response (see pg. 2, Introduction). Thus, Chew et al. provides evidence that immune responses were a recognized obstacle in the AAV-CRISPR/Cas setting and that immunosuppressive treatment was a known strategy to improve effectiveness of such systems.
Regarding Claim 52, Chew et al. demonstrated that administration of an immunosuppressant prior to an AAV CRISPR/Cas9 system resulted in positive suppression of host immune response (see pg. 6-7, AAV-CRISPR-Cas9 does not evoke extensive cellular damage, Discussion; pg. 17, Immunosuppression; Fig. 14(a-e)).
Pyle et al. and Chew et al. do not expressly teach the specific immunosuppressive agents as now claimed.
Byrne et al. teach use of immunosuppressive agents such as anti-CD20 antibody and rapamycin prior to the administration of AAV gene therapy constructs to allow for re-dosing of such constructs (see pg. 1-3, Summary of the Invention). Byrne et al. expressly teach administering a combination of immunosuppressants comprising rituximab (anti-CD20 antibody), rapamycin (sirolimus), and methylprednisolone (see pg. 42, Immunosuppression protocol and ERT). Byrne et al. thus evidences that a skilled artisan would have recognized use of a multi-agent immunosuppressive regimen including rapamycin and anti-CD20-directed therapy, together with a corticosteroid component, to modulate host immune responses to AAV therapy.
Byrne et al. demonstrated a reduced immune response with use of immunosuppressive agents that support the likelihood of successfully administering AAV vectors under immunosuppressive conditions (see pg. 44, Functional measures). Byrne is relied upon for teachings regarding modulation of host immune responses to AAV therapy, and not for the specific underlying disease indication exemplified therein.
Byrne et al. does not expressly teach prednisone.
Cramer et al. taught that administration of prednisone prior to AAV therapy suppresses the immune system in a manner which can aid in the long-term transgene expression (see Methods, Prednisone treatment; Results, Prednisone suppresses T-cell infiltrates in AAV-transduced muscle; Discussion). Cramer therefore teaches that prednisone was a known corticosteroid used in the AAV skeletal-muscle context to suppress immune-mediated effects relevant to vector persistence and expression.
It would have been prima facie obvious to a skilled artisan at the time of filing to utilize immunosuppressants as discussed in Chew et al. within the methods suggested by Gersbach et al. and Pyle et al. in order to increase the likelihood of successful AAV CRISPR/Cas9 gene therapy results by inhibiting detrimental host immune responses. A skilled artisan would have expected successful implementation of such elements because Chew et al. demonstrates successful immune modulation within CRISPR-Cas gene therapy systems similar to those suggested by Gersbach et al. and Pyle et al.
Furthermore, a skilled artisan would have recognized that prednisone would have been a suitable corticosteroid substitute within the AAV immunosuppressive framework of Byrne et al. because Cramer et al. demonstrated that prednisone was a known immunosuppressive corticosteroid used in the same general AAV skeletal-muscle therapeutic context to suppress T-cell infiltration and support sustained expression. Thus, it would have been prima facie obvious to a skilled artisan at the time of filing to administer the claimed combination of rapamycin, prednisone, and anti-CD20 antibody to obtain immunosuppression prior to AAV administration as suggested by Byrne et al. in view of Cramer et al. Selection of prednisone as the corticosteroid component would have represented no more than a predictable variation among known corticosteroid options used for AAV-associated immune suppression.
Taken together, these references render the claimed invention prima facie obvious based on a preponderance of the evidence (absent secondary considerations). In particular, the cited combination teaches or fairly suggests: (1) DMD/BMD-targeted CRISPR editing of dystrophin (Pyle); (2) AAV delivery of CRISPR components for DMD-related therapy (Gersbach); (3) recognition that AAV-CRISPR systems can provoke host immune responses and that immunosuppression prior to vector administration can mitigate such responses (Chew); and (4) known multi-agent AAV immunosuppressive regimens including rapamycin, anti-CD20-directed therapy, and a corticosteroid component, with prednisone specifically taught in the AAV skeletal-muscle context (Byrne; Cramer).
Notably, the claims do not require successful re-dosing in every embodiment, since Claim 41 recites “one or more doses” and thus encompasses single-dose administration as well. No persuasive evidence of secondary considerations has been presented. Applicant does not appear to expressly assert that the presently claimed combinations yield unexpected results relative to the closest prior art in a manner sufficient to outweigh the prima facie case, nor has applicant otherwise established secondary considerations commensurate in scope with the claims.
Claim 58 is rejected under 35 U.S.C. 103 as being unpatentable over Pyle et al. (WO 2017/139505 A2; 17 August 2017), in view of Gersbach et al. (WO 2014/197748 A1; 11 December 2014), Chew et al. (A multifunctional AAV-CRISPR-Cas9 and its host response, Nat Methods 13, 868-874 (2016)), Byrne et al. (WO 2015/164758 A1; 29 October 2015), and Cramer et al. (Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone, Hum Gene Ther. 2017 Jun;28(6):493-509) as applied to Claim 41 above, and in further view of Zhang et al. (WO 2014/093622 A2; 19 June 2014).
The previously cited references do not expressly teach vector dosage amounts in the claimed range (between 106 and 1014 vector genomes/kg).
Zhang et al. teaches use of AAV vectors comprising CRISPR/Cas9 constructs for gene therapy purposes (see pg. 2-24, Summary of the Invention). Zhang et al. exemplifies several dosage recommendations for AAVs (e.g. 105 to 1015 vector genomes), including a human dosage of ∼1013 vector genomes ([00194]-[00195]). Zhang et al. also notes that effective dosages can be readily determined by skilled artisans through routine experimentation ([00194]-[00195]).
Absent secondary considerations, the claimed range of vector genome dosages would have been prima facie obvious to a skilled artisan at the time of filing through routine optimization in view of the teachings of Zhang et al. The claimed range is broad and encompasses dosage values that a skilled artisan would have considered result-effective variables in the AAV gene therapy context. Since Claim 58 depends from Claim 41, and Claim 41 remains obvious for the reasons set forth above, addition of a broadly recited dosage range does not render the claim patentable.
No persuasive evidence of secondary considerations has been presented. Applicant does not appear to expressly assert unexpected results for the claimed dosage range or any other rebuttal evidence sufficient to overcome the prima facie case.
Claim Rejections - 35 USC § 103 - Response to Arguments
Argument that the cited references fail to teach or suggest all claim limitations
Applicant argues that the cited references fail to teach or suggest each and every element of the pending claims, particularly the use of AAV vectors and the specific combination of immunosuppressive agents recited in claim 41. This argument is not persuasive because the rejection is based on the combined teachings of the cited references, not on any single reference alone. Pyle teaches the DMD/BMD dystrophin editing framework, including the intron 44/intron 55 targeting strategy and related deletion endpoints. Gersbach teaches use of AAV vectors to deliver CRISPR components for DMD-related therapy. Chew teaches that AAV-CRISPR/Cas systems can provoke host immune responses and that immunosuppression administered prior to vector delivery can suppress such responses. Byrne teaches multi-agent immunosuppressive regimens for AAV therapy including rapamycin and anti-CD20/rituximab together with a corticosteroid component. Cramer teaches that prednisone was known for administration prior to AAV therapy in skeletal muscle to suppress immune-mediated effects and aid long-term expression. Thus, the references are relied upon for their complementary teachings, which is proper under 35 U.S.C. 103.
Argument that Gersbach does not teach the claimed immunosuppressive combination
Applicant argues that Gersbach does not teach the claimed immunosuppressive combination. This argument is not persuasive because Gersbach is not relied upon for the immunosuppressive regimen, but rather for the use of AAV delivery of CRISPR components in the DMD setting. The immunosuppressive teachings are supplied by Chew, Byrne, and Cramer.
Argument that Chew teaches only general immunosuppression and uses FK506 rather than the claimed combination
Applicant argues that Chew teaches only general immunosuppression, and in particular uses FK506, rather than the specific claimed combination. This argument is not persuasive. Chew is relied upon for the teaching that a person of ordinary skill in the art would have recognized that immune responses are a known obstacle in the AAV-CRISPR/Cas setting, and that administration of immunosuppressive treatment prior to AAV delivery was a known approach for reducing such responses. Chew need not teach the exact claimed combination because the specific agent selection is further informed by Byrne and Cramer. Accordingly, the rejection is not based on a mere invitation to explore a general field, but on a combination of references that collectively teach the AAV-CRISPR DMD framework, the immune problem in that framework, and known AAV-associated immunosuppressive solutions.
Argument that Byrne does not teach prednisone and Cramer does not teach the full claimed combination
Applicant argues that Byrne does not teach prednisone, and that Cramer does not teach the full claimed combination. These arguments are not persuasive because Byrne is relied upon for the teaching of a multi-agent immunosuppressive regimen for AAV therapy including rapamycin and anti-CD20/rituximab together with a corticosteroid component, whereas Cramer is relied upon specifically for the teaching that prednisone was a known corticosteroid used in the AAV skeletal-muscle context. Thus, the rejection does not depend on either Byrne or Cramer individually teaching the entire claimed combination.
Argument that there would have been no motivation to substitute prednisone for methylprednisolone
Applicant argues that there would have been no motivation to substitute prednisone for methylprednisolone, asserting that methylprednisolone is more potent. This argument is not persuasive. The rejection does not require a finding that prednisone and methylprednisolone are identical in potency. Rather, the relevant inquiry is whether a person of ordinary skill in the art would have found it obvious to select prednisone, a known corticosteroid used in the same general AAV skeletal-muscle immunosuppression context, as the corticosteroid component of a known multi-agent AAV immunosuppressive regimen. The cited art supports that conclusion. Byrne teaches the desirability of a multi-agent immunosuppressive regimen for AAV therapy including rapamycin and anti-CD20-directed therapy together with a corticosteroid component, and Cramer teaches that prednisone was used to suppress immune-mediated effects in AAV-transduced skeletal muscle. Selection of prednisone as the corticosteroid component would therefore have represented a predictable variation among known corticosteroid options used for AAV-associated immune suppression. Applicant’s citation to relative potency evidence has been considered, but it does not outweigh the express teaching in Cramer that prednisone was suitable in the relevant AAV context.
Argument that the rejection is based on improper hindsight
Applicant argues that the rejection is based on improper hindsight. This argument is not persuasive. The rejection is based on explicit teachings in the cited references and on the problem recognized in the art, namely, applying AAV-delivered CRISPR therapy in DMD-related settings while mitigating known host immune responses to AAV and CRISPR/Cas components. The references collectively provide the DMD/BMD editing strategy, the AAV delivery platform, recognition of immune-response issues in the AAV-CRISPR setting, and known immunosuppressive approaches for AAV-associated therapy. The conclusion of obviousness therefore follows from the prior art itself and not from applicant’s disclosure.
Argument that there would have been no reasonable expectation of success
Applicant argues that the Office has not established a reasonable expectation of success, particularly because Chew uses FK506, Byrne concerns Pompe disease, and CRISPR/Cas cargo may be more immunogenic than GAA. This argument is not persuasive. Absolute predictability is not required; rather, the proper inquiry is whether a person of ordinary skill in the art would have had a reasonable expectation of success. The cited references collectively support such an expectation. Pyle teaches the relevant dystrophin editing strategy, Gersbach teaches AAV delivery of CRISPR components for DMD-related therapy, Chew teaches that immune responses are a recognized issue in the AAV-CRISPR/Cas setting and that immunosuppression can mitigate such responses, Byrne teaches that multi-agent immunosuppressive regimens including rapamycin and anti-CD20-directed therapy can reduce immune barriers to AAV therapy, and Cramer teaches that prednisone can modulate immune-mediated effects in AAV-transduced skeletal muscle. Applicant’s argument that Byrne concerns Pompe disease is not persuasive because Byrne is relied upon for its teaching regarding immune modulation of AAV therapy, not for the specific underlying disease indication. Likewise, applicant’s argument that CRISPR/Cas may be more immunogenic than human GAA does not defeat the rejection, and if anything would have further motivated a skilled artisan to employ known immunosuppressive strategies in the AAV-CRISPR context. Chew directly addresses immune responses in the AAV-CRISPR/Cas setting.
Argument that not all immunosuppressive agents or combinations work equally well and that the claimed combination allows re-dosing
Applicant argues that not all immunosuppressive agents or combinations work equally well, citing the specification as showing that certain regimens do not allow re-dosing of rAAV particles. This argument has been considered but is not persuasive on the present record. The fact that some immunosuppressive agents may perform better than others does not, by itself, establish nonobviousness where the prior art teaches use of immunosuppression in the AAV-CRISPR context and further teaches specific agents relevant to the claimed combination.
Notably, to the extent applicant suggests that the claimed combination yields the unexpected ability to permit re-dosing, such an assertion could in principle be relevant to unexpected results if supported by sufficient comparative evidence against the closest prior art and if commensurate in scope with the claims. However, applicant does not clearly present this as a secondary-considerations argument, and claim 41 does not require re-dosing, instead reciting “one or more doses.” Accordingly, any alleged re-dosing benefit is not commensurate in scope with claim 41 and is not presently persuasive as evidence of unexpected results sufficient to overcome the prima facie case. More generally, applicant does not appear to assert secondary considerations in a developed manner, such as unexpected results, with evidence sufficient to outweigh the prima facie case.
Argument that amendment of claim 41 to recite DMD or BMD overcomes the rejection
Applicant argues that amendment of claim 41 to expressly recite DMD or BMD overcomes the rejection. This argument is not persuasive because Pyle and Gersbach already direct the skilled artisan to DMD-related CRISPR gene editing using AAV-based delivery concepts. The principal issue addressed by the rejection is the obviousness of applying known AAV-associated immunosuppressive approaches to that known therapeutic framework.
Argument regarding claim 58 and Zhang
Applicant argues that Zhang does not specifically teach the claimed dosage range on a vg/kg basis and does not remedy the alleged deficiencies of the base combination. This argument is not persuasive. Claim 58 depends from claim 41, and claim 41 remains obvious for the reasons set forth above. Zhang is additionally relied upon for dosage guidance showing that vector dosage amounts for AAV-CRISPR gene therapy were known result-effective variables subject to routine optimization. The claimed range of 106 and 1014 vector genomes/kg is broad, and applicant has not shown that the claimed dosage range produces unexpected results sufficient to overcome the prima facie case.
Conclusion
Accordingly, applicant’s arguments have been fully considered but are not persuasive, and the rejection of claims 41-54, 56-58 under 35 U.S.C. 103 is maintained.
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 41-54, 56, and 57 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1 of U.S. Patent No. 11,666,666 ('666) in view of Pyle et al. (WO 2017/139505 A2; 17 August 2017), Gersbach et al. (WO 2014/197748 A1; 11 December 2014), Chew et al. (A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods 13, 868-874 (2016)), Byrne et al. (WO 2015/164758 A1; 29 October 2015), and Cramer et al. (Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone. Hum Gene Ther. 2017 Jun;28(6):493-509).
'666 claims a related method for treating Duchenne muscular dystrophy. The claim appears to recite a slightly more specific CRISPR/Cas9 structure that would anticipate the broader, instantly claimed CRISPR/Cas9 structure absent use of AAV gene therapy vectors and immunosuppressive agents (see '666 Claim 1, e.g. introducing a deletion of 700 kb-725 kb).
The teachings of the cited references are outlined above. It would have been prima facie obvious to a skilled artisan at the time of filing to utilize AAV vectors and immunosuppressants within the methods of '666 Claim 1 for the same reasons outlined above in the corresponding prior art rejection. More specifically, Gersbach et al. teach use of AAV vectors comprising CRISPR/Cas9 constructs for DMD-related therapy, Chew et al. teach that AAV-CRISPR/Cas systems may provoke detrimental host immune responses and that immunosuppression administered prior to vector delivery can suppress such responses, Byrne et al. teach multi-agent immunosuppressive regimens for AAV therapy including rapamycin and anti-CD20/rituximab together with a corticosteroid component, and Cramer et al. teach that prednisone was known for use prior to AAV therapy in skeletal muscle to suppress immune-mediated effects and aid long-term expression. Thus, it would have been prima facie obvious to a skilled artisan at the time filing to employ known AAV delivery systems and known AAV-associated immunosuppressive strategies within the closely related DMD CRISPR framework of '666 Claim 1.
Claim 58 is rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1 of U.S. Patent No. 11,666,666 ('666) in view of Pyle et al. (WO 2017/139505 A2; 17 August 2017), Gersbach et al. (WO 2014/197748 A1; 11 December 2014), Chew et al. (A multifunctional AAV-CRISPR-Cas9 and its host response. Nat Methods 13, 868-874 (2016)), Byrne et al. (WO 2015/164758 A1; 29 October 2015), and Cramer et al. (Induction of T-Cell Infiltration and Programmed Death Ligand 2 Expression by Adeno-Associated Virus in Rhesus Macaque Skeletal Muscle and Modulation by Prednisone. Hum Gene Ther. 2017 Jun;28(6):493-509) as applied to Claim 41 above, and in further view of Zhang et al. (WO 2014/093622 A2; 19 June 2014).
The claim would have been prima facie obvious to a skilled artisan at the time filing for the same reasons outlined above in the corresponding prior art rejection. Zhang et al. further teach AAV dosage recommendations for CRISPR/Cas9 gene therapy and note that effective dosages can be readily determined by skilled artisans through routine experimentation. Accordingly, the additionally recited dosage range does not render claim 58 patentably distinct.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Colosi et al. (US 20200362368 A1; effective filing date 5/14/2019). This reference expressly teaches methods of readministering or redosing AAV gene therapy vectors to treat the same disease, including by administering a second AAV vector having a different capsid in order to avoid or evade immune responses to the first administration (see, e.g., [0011]-[0015], [0095]-[0096], [0135]-[0149], [0291]-[0300]). The reference further identifies muscular dystrophy, including Duchenne muscular dystrophy, among the diseases to which such redosing methods may be applied (see, e.g., [0036]-[0037], [0050], [0289]-[0290]), contemplates therapeutic payloads including CRISPR/Cas guide polynucleotides (see, e.g., [0016], [0043], [0048]-[0050]), and describes use of immunosuppressants in connection with the second administration, including sirolimus (rapamycin) and prednisone (see, e.g., [0039], [0298]).
Allowable Subject Matter
Claim 55 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. A search of the prior art found no reference teaching or fairly suggesting the claimed combination of immunosuppressants in the context of the claimed method.
Conclusion
No claim is allowed.
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/CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633
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