DETAILED ACTION
Claims 1-20, submitted 20 July 2023, are pending in the application. Claims 18-20 are withdrawn. Claims 1-16 are under examination in the instant Office Action. Claim 17 is drawn to allowable subject matter.
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
Applicant’s election of Group I, claims 1-17, in the reply filed on 16 February 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 18-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 16 February 2026.
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.
Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ciani et al. (US PG-PUB 2019/0091207 A1) in view of Georgievska et al. ("AZD 1080, a novel GSK 3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans." Journal of neurochemistry 125.3 (2013): 446-456.).
Ciani discloses a method of treating a CDKL5 disorder by administering tideglusib or a derivative thereof (paragraph 0085). This reference does not teach the method wherein the compound administered is selected from ivabradine, solifenacin, AZD1080, crenigacestat, and any combination thereof but does teach that tideglusib is a GSK3β inhibitor (paragraph 0194). While Ciani does not teach the required compounds, this deficiency is overcome, in part, by the teachings of Georgievska which teaches that AZD1080 is a potent GSK3 inhibitor (Abstract) and displays selectivity against cdk5 (pg. 449, Section “AZD1080 is potent and selective in vitro”, Right Col., 1st paragraph).
A person having ordinary skill in the art would have been motivated to modify the teachings of Ciani with the teachings of Georgievska to treat a disease or disorder caused by abnormal CDKL5 expression in a subject because Georgievska teaches “AZD1080 reverses synaptic plasticity and functional deficits in a dysfunctional neuronal system and the efficacious effect is likely because of modification of pathways downstream of GSK3” (pg. 454, Section “Discussion”, Right Col., 2nd paragraph) which is closely related to CDK5 (pg. 449, Section “AZD1080 is potent and selective in vitro”, Right Col., 1st paragraph). Thus, an ordinarily skilled artisan would have had a reasonable expectation of success because it would have been prima facie obvious to one skilled in the art to substitute the GSK3 inhibitor, tideglusib, with AZD1080, which also affects cdk5, to arrive at the instantly claimed invention.
With respect to claim 2, Georgievska teaches that oral administration of AZD1080 had a good bioavailability in rat subjects making it attractive for further in vivo testing (pg. 451, Section “Central target engagement with AZD1080 in rats”, Left Col., 1st paragraph). Thus, it would have been prima facie obvious to administer AZD1080 as a single pharmaceutical composition formulated for oral administration.
With respect to claim 3, Ciani teaches wherein “Mutations in the X-linked cyclin-dependent kinase-like 5 ( CDKL5 ) gene and resulting protein have been found in individuals with a rare neurodevelopmental disorder characterized by early-onset epileptic encephalopathy” (paragraph 0078). Which identifies CDKL5 as a genetic disease or disorder that effects the resulting protein.
Regarding claim 4, Ciani teaches wherein the disease or disorder can be a CDKL5 deficiency and/or Rett Syndrome (paragraph 0051).
Regarding claims 5 and 6, Ciani states “CDKL5 disorder affects primarily females due to the X-chromosome location of the CDKL5 gene” and also recites “Males can also be affected, although with a lower incidence, and typically have a more severe phenotype (paragraph 0078). Therefore, it would have been prima facie obvious to one skilled in the art to treat a CDKL5 deficiency disorder in both males and females through administration of AZD1080.
With respect to claims 7 and 8, Ciani teaches administration to age ranges from 1 to 21 years (paragraph 0146). Hence, it would have been prima facie obvious to treat a CDKL5 deficiency disorder to patients younger than 25 years old and also patients younger than 10 years old.
With respect to claim 9, Ciani teaches a method of treating a disease or disorder can be a CDKL5 deficiency and/or Rett Syndrome (paragraph 0051) through administration of a GSK3β inhibitor (paragraph 0194). Ciani does not teach wherein the compound administered is selected from ivabradine, solifenacin, AZD1080, crenigacestat, and any combination thereof. However, Georgievska teaches that AZD1080 is a potent GSK3 inhibitor (Abstract) and displays selectivity against cdk5 (pg. 449, Section “AZD1080 is potent and selective in vitro”, Right Col., 1st paragraph).
A person having ordinary skill in the art would have been motivated to modify the teachings of Ciani with the teachings of Georgievska to treat CDKL5 deficiency disorder in a subject because Georgievska teaches “AZD1080 reverses synaptic plasticity and functional deficits in a dysfunctional neuronal system and the efficacious effect is likely because of modification of pathways downstream of GSK3” (pg. 454, Section “Discussion”, Right Col., 2nd paragraph) which is closely related to CDK5 (pg. 449, Section “AZD1080 is potent and selective in vitro”, Right Col., 1st paragraph). Thus, an ordinarily skilled artisan would have had a reasonable expectation of success because it would have been prima facie obvious to one skilled in the art to substitute the GSK3 inhibitor, tideglusib, with AZD1080, which also affects cdk5, to arrive at the instantly claimed invention.
With respect to claim 10, Georgievska teaches that oral administration of AZD1080 had a good bioavailability in rat subjects making it attractive for further in vivo testing (pg. 451, Section “Central target engagement with AZD1080 in rats”, Left Col., 1st paragraph). Thus, it would have been prima facie obvious to administer AZD1080 as a single pharmaceutical composition formulated for oral administration.
Regarding claim 11, Ciani teaches wherein CDKL5 mutation refers to any
change in the nucleotide sequence of the coding region of the CDKL5 protein (paragraph 0068). Additionally, Ciani teaches that CDD is a result of lacking and/or having a mutated or otherwise dysfunctional CDKL5 gene and/or protein (paragraph 0049).
With respect to claim 12, Ciani teaches wherein “Mutations in the X-linked cyclin-dependent kinase-like 5 ( CDKL5 ) gene and resulting protein have been found in individuals with a rare neurodevelopmental disorder characterized by early-onset epileptic encephalopathy” (paragraph 0078). Which identifies CDKL5 as a genetic disease or disorder that effects the resulting protein.
Regarding claims 13 and 14, Ciani states “CDKL5 disorder affects primarily females due to the X-chromosome location of the CDKL5 gene” and also recites “Males can also be affected, although with a lower incidence, and typically have a more severe phenotype (paragraph 0078). Therefore, it would have been prima facie obvious to one skilled in the art to treat a CDKL5 deficiency disorder in both males and females through administration of AZD1080.
With respect to claims 15 and 16, Ciani teaches administration to age ranges from 1 to 21 years (paragraph 0146). Hence, it would have been prima facie obvious to treat a CDKL5 deficiency disorder to patients younger than 25 years old and also patients younger than 10 years old.
Allowable Subject Matter
Claim 17 is allowed.
The following is a statement of reasons for the indication of allowable subject matter: Claim 17 is deemed novel and unobvious over the prior art.
The closest prior art is Georgievska et al. ("AZD 1080, a novel GSK 3 inhibitor, rescues synaptic plasticity deficits in rodent brain and exhibits peripheral target engagement in humans." Journal of neurochemistry 125.3 (2013): 446-456.) which teaches the single agent of AZD1080 in an oral composition for administration (pg. 451, Section “Central target engagement with AZD1080 in rats”, Left Col., 1st paragraph).
This reference neither teaches nor renders obvious the combination of agents wherein the at least 2 agents are AZD1080 with ivabradine, solifenacin, or crenigacestat or the salts of any of the foregoing which would lead to a similar invention as that of the applicants.
Therefore, the prior art neither anticipates, nor reasonably makes obvious claim 17 and thus, the claim 17 is deemed novel and unobvious over the prior art.
Conclusion
Claim 17 is drawn to allowable subject matter.
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622