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 .
This action is in response to the amendment filed 03/16/2026, in which claims 1, 7, 9 and 16 were amended, claims 2, 15, 27, 29, 40 and 73 were canceled, claim 126 was newly added and claims 24, 41, 48-50, 54-55, 57, 62, 64-67, 71-72 and 99 were withdrawn due to a previous restriction requirement outlined in the Office Action mailed on 12/16/2025. Claims 1, 7, 9, 16 and 126 are currently pending.
Applicant’s arguments have been thoroughly reviewed, but are not persuasive for the
reasons that follow. Any rejection and objections not reiterated in this action have been
withdrawn. This action is NON-FINAL.
Information Disclosure Statement
Receipt of acknowledgment of the information disclosure statement filed on 02/23/2026 have been received and all references have been considered.
Drawings
The previous objection to the drawings has been withdrawn in view of Applicant’s submission of new drawings filed on 03/16/2026.
Response to Amendments - Claim Objections
The previous objection to claim 73 has been withdrawn in view of Applicant’s cancelation of the claim in the amendments filed on 03/16/2026.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
This is a NEW rejection necessitated by the amendments to the claims filed on 03/16/2026.
Claims 1, 7, 9, 16 and 126 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Enablement is considered in view of the Wands factors (MPEP 2164.01(A)). These include: the breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and the quantity of experimentation needed to make or use the invention. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of the invention: The claims are drawn to a method of treating a subject having Prader Willi Syndrome (PWS) or Prader- Willi-like disorder comprising administering to the subject a DNA Targeting System that targets the 15q11-13 PWS-associated locus. The nature of the invention is complex in that the function of treating a disease in a subject, specifically treating Prader Willi Syndrome or a Prader Willi-like disorder, is not specified.
Breadth of the claims: The claims encompass: a method of treating a cell, including a human cell, having Prader Willi Syndrome (PWS) or Prader Willi-like disorder comprising administering to the subject a DNA Targeting System that targets the 15q11-13 PWS-associated locus. The claims, and species elected from the species election, are drawn to the paternal Prader Willi Syndrome locus as well as a repressor system targeting this locus.
The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims.
Guidance of the specification and existence of working examples: The specification teaches that a patient with paternal deletions or mutations within 15q11.2-13 can present with PWS while retaining functional copies of these genes on the maternal allele [0005]. The specification continues to teach that seventy percent of PWS cases are cause by a large 4-5Mb deletion on the paternal allele [0005]. The specification teaches that twenty-five percent of PWS cases are caused by uniparental maternal disomy (UPD) 15, in which two copies of the maternal chromosome are inherited instead of one copy frorn each parent and infrequently, PWS is caused by mutations or microdeletions of the PWS imprinting center [0005]. The specification continues to teach that exceedingly rare cases of PWS are caused by paternal microdeletions of PWS critical region genes, including SNORD116 [0005]. The specification teaches initial screening of the PWS region was performed in human induced pluripotent stem cells (iPSCs) using several imprinted genes within the 15q11-13 locus, including the paternally-expressed coding genes MAGEL2, NDN and SNURF-SNRPN, along with numerous noncoding RNAs, including snoRNA clusters SNORD and SNORD115 and SNORD116 [000219-000220]. The specification continues that a human iPS cell line was used to construct the maternal and paternal SNRPN-2A-GFP reporter lines by retrovirally reprogramming RVR-iPSCs from BJ fibroblasts [000222]. The specification teaches in example 2, that a DNA repressor system was constructed using a dCas9-KRAB with a set of four gRNAs to successfully knockdown SNRPN mRNA expression in the paternally-tagged SNPRN-GFP iPS cells [000236]. Example 3 of the specification teaches that by targeting the region around positions +24022 and +35734 with the DNA repressor system resulted in increased GFP signal indicating increased SNRPN expression [000240]. Example 4 of the specification teaches the material SNRPN-GFP iPS cells targeted with a DNA targeted activator system, comprising a VP64dCas9VP64 [000244]. The specification teaches that gRNA targeting around positions -126023 and -92065 within the imprinting center were capable of sufficient up-regulating maternal SNRPN [000245].
While Applicant has successfully showed increased expression of SNRPN in iPS cells when the iPSCs have been constructed to contain the a SNRPN stop codon to induce the phenotype of Prader-Willi Syndrome by administering a DNA targeting system, either a Targeted Activator system or Targeted Repressor system (Examples 2-5). The claims, or working examples, do not include which deletions of the paternal copy are present to understand the exact type of PWS is being tested on.
To date there is no evidence in the art or the specification teaching Prader-Willi syndrome or a Prader Willi-like disorder in any species other than human. Any genetically-based Prader-Willi syndrome or a Prader Willi-like disorder observed outside of humans is engineered via mutation as Applicant has done in the instant specification within iPSCs.
Predictability and state of the art: The prior art teaches that while there is no cure for Prader-Willi syndrome, major strides to improve quality of life have been made since the introduction of more sensitive genetic testing modalities which has allowed early diagnosis and intervention (Cataletto et al; Int J Pediatr Endocrinol. 2011 Oct 18;2011(1):12, Pages 1-13; Page 10, Column 2).
More current art, such as Nemoto et al (Nat Commun. 2025 Oct 28;16(1):9442, Pages 1-12), teaches Prader-Willi syndrome (PWS) results from the loss of function of paternally expressed genes (PEGs) within the chromosome 15q11-13 imprinted region wherein the primary clinical manifestations of PWS include hyperphagia, hypogonadism, and short stature due to growth hormone deficiency, and these phenotypes have been thought to be closely related to hypothalamic dysfunction; however, little is known about the cellular and molecular pathophysiology (Page 1, Column 1). Nemoto teaches that the limits of their experimentation include the unpredictability of utilizing the CRISPRCas targeting systems within humans for the successful treatment of Prader-Willi syndrome due unknown stability of imprinting control in the long term as well as limitation in translational applications (Page 8, Column 1).
Kim et al (Translational Research, 208, 105–118) teaches that PWS is considered as a contiguous chromosomal microdeletion syndrome and a prototype for "genomic disorder”, specifically the majority of PWS patients have a large deletion (~6 Mb) of the paternal chromosome 15ql l-q13, which include roughly the entire paternal locus (Page 106, Column 2). Kim teaches the SNORD116 is part of the paternal Prader Willis deletion (Page 111, Column 1).
Cassidy et al (Genet Med. 2012 Jan;14(1):10-26) teaches that the Prader Willis type I and II both show deletion of the entire PWS region, including SNRPN and SNORD genes, of the paternal copy (Page 16, Figure 3).
Therefore, it would be impossible to deliver a targeting repressor system to the paternal copy if the genes are deleted in the Prader Willis locus. It is unclear from the current claims, and the working examples, if the cell or subject comprising the Prader Willis disease has different deletions of the paternal copy that would enable the invention to be successful.
Amount of experimentation necessary: In order to practice the claimed invention, an immense amount of experimentation would be required. As disclosed above, the specification itself provides description of a method of administering to a cell with a genetic modification causing Prader Willi Syndrome or a Prader Willi-like disorder, a composition comprising a DNA targeting system wherein the DNA targeting system targets the 15q11-13 PWS-associated locus. The specification does not teach how the DNA targeting system is capable of being administered effectively to a subject in order to treat Prader Willi Syndrome or a Prader Willi-like disorder. Therefore, experiment could be conducted, but in view of the specification there does not appear to be any amount of experimentation that would be sufficient to reliably produce the exact product of the invention. Therefore, it would require immense amount of unpredictable experimentation to practice the claimed invention with such variants in the possible result.
In view of the breadth of the claims and the lack of guidance provided by the specification as well as the unpredictability of the art, the skilled artisan would have required an undue amount of experimentation to make and/or use the claimed invention. Therefore, claims 1, 7, 9, 16 and 126 are not considered to be fully enabled by the instant disclosure.
Response to Amendments - Claim Rejections - 35 USC § 112
The previous rejection of claim 27 under 35 U.S.C. 112(b) has been withdrawn in view of Applicant’s cancelation of the claim in the amendments filed on 03/16/2026.
The previous rejection of claims 1, 7, 9, 16 and 126 under 35 U.S.C. 112(a) has been withdrawn in view of the amendments filed on 03/16/2026.
Although the previous rejection has been withdrawn, Applicant’s arguments have still been fully considered but have not been found persuasive. Applicant argues that the amendments to the claims are sufficient for the withdrawn of the previous 112(a) rejection.
However, the issue still stands due to the recitation of the phrase “a method of treating” in the instant claim 1 as well as the addition of new claim 126 reciting “wherein the cell is in a human subject”.
Response to Amendments - Claim Rejections - 35 USC § 102
The previous rejection of claims 1 and 9 under 35 U.S.C. 102(a)(1) has been withdrawn in view of Applicant’s amendments to the claims filed on 03/16/226.
Response to Arguments - Claim Rejections - 35 USC § 103
The previous rejection of claims 2, 7, 15, 16, 27, 29 and 40 under 35 U.S.C. 103 has been withdrawn in view of Applicant’s amendments to the claims filed on 03/16/2026.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEXANDRA ROSE LIPPOLIS whose telephone number is (703)756-5450. The examiner can normally be reached Monday-Friday, 8:00am to 5:00pm EST.
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/ALEXANDRA ROSE LIPPOLIS/Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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