DETAILED ACTION
This action is in reply to papers filed 6/23/2026.
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 .
Examiner’s Note
All paragraph numbers throughout this office action, unless otherwise noted, are from the US PGPub of this application US20230265453A1, Published 8/24/2023.
Election/Restrictions
Applicant’s election without traverse of Group II, in the reply filed on 6/23/2026 is acknowledged. Election was made without traverse in the reply filed on 6/23/2026. Claims 17-27 and 31-46 are pending and examined herein.
Claim Objections
Claim 22 objected to because of the following informalities: Claim 22 recites, inter alia, “…wherein individual has one or more…” The term ‘the’ is missing between ‘wherein’ and ‘individual’. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Prior Art Rejection 1
Claim(s) 17-18, 22-23, 26-27, 37-38 and 43-45 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Tagliatela et al. (PgPub US20190024120A1, Published 12/31/2019).
Regarding claim 17 and claim 43, Tagliatela et al. discloses a method of treating an individual with an encephalopathy (Pg. 2, para. 8) comprising administering to the individual a therapeutically effective amount of an adeno-associated virus (AAV) particle (Pg. 6, para. 38), comprising a nucleic acid comprising a sequence encoding an STXBP1 gene product (Pg. 1-2, para. 6), wherein the individual has one or more mutations in a STXBP1 gene causing disease in the individual (Pg. 2, para. 11).
Regarding claim 18 and claim 45, Tagliatela et al. discloses the individual has STXBPl encephalopathy (Pg. 34, para. 181).
Regarding claim 22 and claim 44, Tagliatela et al. discloses the individual has one or more haploinsufficiencies or mutations s in the STXBP1 gene (Pg. 2, para. 11).
Regarding claim 23, Tagliatela et al. discloses wherein the individual is an infant,
child, or adolescent (Pg.35-36, para. 190).
Regarding claim 26, Tagliatela et al. discloses wherein the AAV particle is
administered by injection outside of the brain (Pg.2 3, para. 102).
Regarding claim 27, Tagliatela et al. discloses prior to administering the AAV particle to the individual, detecting a mutation the one or more mutations in STXBP1 in the individual (Pg. 23, para. 102).
Regarding claim 37, Tagliatela et al. discloses SEQ ID NO: 40 which is 100% identical to SEQ ID NO: 1.
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Regarding claim 38, Tagliatela et al. discloses the sequence encoding the STXBPl gene
product is operably linked to one or more regulatory sequences selected from the group
consisting of CAG, CBA, EFla and CMV (Pg. 30, para. 145).
Accordingly, Tagliatela et al. anticipates the claimed invention.
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.
Prior Art Rejection 2
Claim 20 and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Tagliatela et al. (PgPub US20190024120A1, Published 12/31/2019) as applied to claims 17-18, 22-23, 26-27, 37-38 and 43-45 and further in view of Saitsu et al. (In: Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.)
The teachings of Tagliatela et al. are relied upon as detailed above. However, Tagliatela et al. fails to teach the individual has Ohtahara syndrome with mutated STXBP (as in claim 20).
Before the effective filing date of the claimed invention, Saitsu et al. taught that in order to delineate the clinical spectrum of patients with STXBP1 mutations, STXBP1 was analyzed in 29 cases of cryptogenic Ohtahara syndrome (OS). Saitsu teaches no brain malformations were found in any of the cases. Seven novel heterozygous mutations were found in nine OS cases (the same mutation was found in three cases). The mutations included one missense, one splicing, two frameshift, and three nonsense mutations. A recurrent missense mutation (c.1217G>A, p.R406H) occurred at an evolutionarily conserved amino acid (Figure 1). All the mutations occurred de novo. Collectively, Saitsu teaches STXBP1 aberrations account for about one-third of individuals with OS (14 out of 43). Saitsu adds that these data showed that STXBP1 mutations are a major genetic cause of cryptogenic OS (as in claim 20 and claim 46) (Abstract; Pg. 2, STXBP1 Mutation Is a Major Genetic Cause of OS).
When taken with the teachings of Saitsu et al., one of ordinary skill in the art would have found it prima facie obvious to treat a patient having Ohtahara syndrome because using the method of treating in Tagliatela because Saitsu observed that 14 out of 43 patients with STXBP1 aberrations had Ohtahara syndrome. Thus, it would have been obvious for one of ordinary skill in the art to administer, inter alia, a composition comprising a transgene encoding STXBP1.
Thus, the modification would have been prima facie obvious.
Prior Art Rejection 3
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over Tagliatela et al. (PgPub US20190024120A1, Published 12/31/2019) as applied to claims 17-18, 22-23, 26-27, 37-38 and 43-45 and further in view of Rezazadeh et al. (Epilepsy Behav. 2019 Mar: 92:121-124.)
The teachings of Tagliatela et al. are relied upon as detailed above. However, Tagliatela et al. fails to teach the individual is an adult (as in claim 24).
Before the effective filing date of the claimed invention, Rezazadeh et al. investigated 5 unrelated patients with different de novo mutations in STXBP1. Rezazadeh conducted an online survey through Facebook to identify the incidence of bruxism (BRX) in these patients. Four out of 5 patients (80%) presented with awake BRX (A-BRX). Rezazadeh teaches three out of 5 patients were adults (Abstract; Table 1).
When taken with the teachings of Rezazadeh et al., one of ordinary skill in the art would have found it prima facie obvious to treat an adult patient having STXBP1 mutations because Rezazadeh teaches 3/5 patients having different de novo mutations in STXBP1 were adults.
Thus, it would have been obvious for one of ordinary skill in the art to administer, inter alia, a composition comprising a transgene encoding STXBP1 to an adult.
Thus, the modification would have been prima facie obvious.
Prior Art Rejection 4
Claim 36 is rejected under 35 U.S.C. 103 as being unpatentable over Tagliatela et al. (PgPub US20190024120A1, Published 12/31/2019) as applied to claims 17-18, 22-23, 26-27, 37-38 and 43-45 and further in view of Nonnenmacher et al. (PgPub US20210380969A1, Filed 10/2/2019)
The teachings of Tagliatela et al. are relied upon as disclosed above. However, Tagliatela et al. fails to teach the AAV particle is administered by injection into brain tissue (as in claim 25) or that the particle is selected from the AAV particles listed in claim 36.
Before the effective filing date of the claimed invention, Nonnenmacher et teach methods of method for treating a disease, disorder and/or condition, including encephalopathies, in a human subject, comprising administering to the subject an AAV particle to a brain tissue of the subject (Pg. 16, para. 171; Pg. 16, para. 185; Pg. 18, para. 189). Nonnenmacher teaches the particle is AAVPHP.B (as in claim 36).
When taken with the teachings of Nonnenmacher et al., one of ordinary skill in the art would have found it prima facie obvious to administer to a patient having an STXBP1 causing disease or disorder, a transgene encoding STXBP1 via a direct brain injection because Nonnenmacher et al. observed success when administering to a subject an AAV particle to a brain tissue of the subject. Moreover, the skilled artisan would have found it prima facie obvious to use the AAVPHP.B particle as Nonnenmacher et al. teaches its suitability for such use.
Prior Art Rejection 5
Claim(s) 31 and 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over Tagliatela et al. (PgPub US20190024120A1, Published 12/31/2019), Saitsu et al. (In: Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.) and Nonnenmacher et al. (PgPub US20210380969A1, Filed 10/2/2019)
Tagliatela et al. teaches a method of treating an individual with encephalopathies, including STXBPl encephalopathy (as in claim 39) (Pg. 34,para. 181). comprising administering to the individual a therapeutically effective amount of an adeno-associated virus (AAV) particle (Pg. 6,para. 38) comprising a nucleic acid comprising a sequence encoding an STXBP1 gene product (Pg.2 ,para. 6), wherein the individual has one or more mutations in a STXBP1 gene causing disease in the individual (Pg. 2-3,para. 11). Tagliatela teaches the sequence encoding the STXBPl gene product is operably linked to one or more regulatory sequences selected from the group consisting of CAG, CBA, EFla and CMV (as in claim 42) (Pg. 30, para. 145).
Tagliatela et al. teaches the nucleic acid is SEQ ID NO: 40 which is 100% identical to SEQ ID NO: 1 (as further in claim 31).
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However, Tagliatela et al. fails to teach the individual has Ohtahara syndrome with mutated STXBP (as in claim 40).
Before the effective filing date of the claimed invention, Saitsu et al. taught that in order to delineate the clinical spectrum of patients with STXBP1 mutations, STXBP1 was analyzed in 29 cases of cryptogenic Ohtahara syndrome (OS). Saitsu teaches no brain malformations were found in any of the cases. Seven novel heterozygous mutations were found in nine OS cases (the same mutation was found in three cases). The mutations included one missense, one splicing, two frameshift, and three nonsense mutations. A recurrent missense mutation (c.1217G>A, p.R406H) occurred at an evolutionarily conserved amino acid (Figure 1). All the mutations occurred de novo. Collectively, Saitsu teaches STXBP1 aberrations account for about one-third of individuals with OS (14 out of 43). Saitsu adds that these data showed that STXBP1 mutations are a major genetic cause of cryptogenic OS (as in claim 40) (Abstract; Pg. 2, STXBP1 Mutation Is a Major Genetic Cause of OS).
And although Tagliatela teach use of an AAV particle to deliver the nucleic acid, neither Tagliatela et al. nor Saitsu teach the particle is AAVPHP.B (as in claim 41).
Before the effective filing date of the claimed invention, Nonnenmacher et teach methods of method for treating a disease, disorder and/or condition, including encephalopathies, in a human subject, comprising administering to the subject an AAV particle to a brain tissue of the subject (Pg. 16, para. 171; Pg. 16, para. 185; Pg. 18, para. 189). Nonnenmacher teaches the particle is AAVPHP.B (as in claim 41).
The combination of prior art cited above in all rejections under 35 U.S.C.103 satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1,148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 389, 82 USPQ2d 1385 (2007): "Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) "Obvious to try" - choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention."
In the present situation, rationales A and G are applicable. Before the effective filing date of the claimed invention, it would have been prima facie obvious to an artisan of ordinary skill to combine the teachings of Tagliatela et al., wherein Tagliatela teaches a method of treating an individual with an STXBP1 causing disease or disorder comprising administering to the individual a therapeutically effective amount of an adeno-associated virus (AAV) particle, comprising a nucleic acid comprising a sequence encoding an STXBP1 gene product , wherein the individual has one or more mutations in a STXBP1 gene causing disease in the individual, with the teachings of Saitsu, wherein Saitsu teaches STXBP1 aberrations account for about one-third of individuals with OS, with a reasonable expectation of arriving at the claimed invention.
That is, one of ordinary skill in the art would have found it prima facie obvious to treat the OS of Saitsu et al. with the treatment method of Tagliatela with a reasonable expectation of arriving at the claimed invention. Moreover, the skilled artisan would have found it prima facie obvious to contain the nucleic acid encoding STXBP1 in an AAVPHP.B particle because Nonnenmacher teaches it use in method for treating a disease, disorder and/or condition, including encephalopathies.
Thus, the teachings of the cited prior art in the obviousness rejection above provide the requisite teachings and motivations with a clear, reasonable expectation. The cited prior art meets the criteria set forth in both Graham and KSR.
Therefore, the claimed invention, as a whole, was clearly prima facie obvious
Authorization to Initiate Electronic Communications
The examiner may not initiate communications via electronic mail unless and until applicants authorize such communications in writing within the official record of the patent application. See M.P.E.P. § 502.03, part II. If not already provided, Applicants may wish to consider supplying such written authorization in response to this Office action, as negotiations toward allowability are more easily conducted via e-mail than by facsimile transmission (the PTO's default electronic-communication method). A sample authorization is available at § 502.03, part II.
Conclusion
No claim is allowed.
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/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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