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
1. Applicant’s election without traverse of Group I in the reply filed on November 25, 2025 is acknowledged.
2. Claims 36-40, 48-50, 62 and 72 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention(s), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on November 25, 2025.
3. Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 are under examination.
Sequence compliance
4. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821 (a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825. Specifically, no sequence identification has been provided for the nucleic acid sequences presented at p. 90 of the instant specification. In case these sequences are new, Applicant needs to provide a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, a substitute paper copy of that “Sequence Listing”, an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 (e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO: ) be made in the specification and claims wherever a reference is made to that sequence. See MPEP 2422.04.
Specification
5. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code, pp. 92-93. 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.
6. The use of trade names or marks used in commerce, has been noted in this application, pp. 50-51. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
7. Claim 10 is objected to because of the following informalities:
The claim recites “DYRK1A” and “APP” without first providing the full name of the terms. It is suggested that the terms be spelled out at their first use and in all independent claims so that it is clearly understood what they stand for. Appropriate correction is suggested.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
8. Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 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.
9. The terms “reducing” and “decreasing” in claim 1 are relative terms which render the claim indefinite. The terms “to reduce” and “to decrease” not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Providing a point of reference or comparison within the claim would obviate this ground of rejection.
10. Similarly, the term “increased” in claims 2, 4 and 12, and the term “increase” in claim 10 is a relative term which renders the claims indefinite. Providing a point of reference or comparison within the claims would obviate this ground of rejection.
11. Claims 1, 10, 22 and 26 are vague and ambiguous for reasons that follow. The claims recite a critical feature of the invention, which is description of the compound to be administered, as “a polynucleotide sequence encoding a Fragile X mental retardation protein (FMRP) polypeptide or a fragment thereof,” emphasis added. It is not clear and cannot be determined from the claims or the specification as failed whether “fragment thereof” refers to the polynucleotide or to the polypeptide. This renders the claims indefinite.
12. Applicant is advised that one of the purposes of the 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph is to provide a clear warning to others as to what constitutes infringement of the patent (see, e.g., Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000). The test for definiteness under 35 U.S.C. § 112, second paragraph, is whether “those skilled in the art would understand what is claimed when the claim is read in light of the specification.” Orthokinetics, Inc. v. Safety Travel Chairs, Inc., 806 F .2d 1565 (Fed. Cir. 1986) (citations omitted).
In precedential decision Ex parte Kenichi Miyazaki, Appeal 2007-330, BPAI stated “In particular, rather than requiring that the claims are insolubly ambiguous, we hold that if a claim is amendable to two or more plausible claim constructions, the USPTO is justified in requiring the applicant to more precisely define the metes and bounds of the claimed invention by holding the claim unpatentable under 35 U.S.C. § 112, second paragraph.”
Further, the federal Circuit stated in Halliburton Energy Servs.:
When a claim limitation is defined in purely functional terms, the task of determining whether that limitation is sufficiently definite is a difficult one that is highly dependent on context (e.g., the disclosure in the specification and the knowledge of a person of ordinary skill in the relevant art area). We note that the patent drafter is in the best position to resolve the ambiguity in the patent claims, and it is highly desirable that patent examiner demand that applicants do so in appropriate circumstances so that the patent can be amended during prosecution rather than attempting to resolve the ambiguity in litigation.
Halliburton Energy Servs. V. M-ILLC 514 F .3d 1244, 1255 (Fed. Cir. 2008) (emphasis added).
13. Claims 4 and 5 are vague and ambiguous for reasons that follow. The claims limit the subject matter of claim 2, which encompasses a method of contacting a cell comprising an increased level of DYRK1A and/or APP with an expression vector, to specify that “the increased level of DYRK1A and/or APP is associated with a developmental disorder or neurodegenerative disorder” and further specifically with autism, Fragile X Syndrome, Down syndrome and Alzheimer’s disease. The metes and bounds of the limitation “associated with” cannot be determined from the claims or the specification as filed. Because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of the recited “associated” disease, an artisan cannot determine whether the changes in the cellular levels of DYRK1A and APP would then be included or excluded from the claimed subject matter by the presence of this limitation.
14. Claim 10 is vague and indefinite insofar as it employs the term “disease associated with an increase in a DYRK1A and/or APP polypeptide in a subject” as a limitation. This term is not known in the relevant prior art of record as being associated with well-defined genus of pathological conditions. Moreover, because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of a “disease associated with an increase in a DYRK1A and/or APP polypeptide in a subject”, an artisan cannot determine if a pathology which meets all of the other limitations of a claim would then be included or excluded from the claimed subject matter by the presence of this limitation.
15. Claims 13 and 24 are indefinite for being dependent from indefinite claim.
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.
16. Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 specifically require possession of the fragments of FMRP, polypeptide and polynucleotide, which are suitable for clinical administration. The claims do not require that the recited fragments possess any particular conserved structure or other disclosed distinguishing feature. Thus, the claims are drawn to a genus of fragments of polypeptides and nucleic acids that is defined only by limited structural similarity to the full length of FMRP. However, the instant specification fails to describe the entire genus of fragments, which are encompassed by these claims.
MPEP §2163(I)(A) states:
“The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional or known in the art. Consider the claim "A gene comprising SEQ ID NO:1." The claim may be construed to include specific structures in addition to SEQ ID NO:1, such as a promoter, a coding region, or other elements. Although SEQ ID NO:1 is fully disclosed, there may be insufficient description of other structures embraced by the claim (e.g., promoters, enhancers, coding regions, and other regulatory elements).”
“An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. For example, the amino acid sequence of a protein along with knowledge of the genetic code might put an inventor in possession of the genus of nucleic acids capable of encoding the protein, but the same information would not place the inventor in possession of the naturally-occurring DNA or mRNA encoding the protein. See In re Bell, 991 F.2d 781, 26 USPQ2d 1529 (Fed. Cir. 1993); In re Deuel, 51 F.3d 1552, 34 USPQ2d 1210 (Fed. Cir. 1995) (holding that a process could not render the product of that process obvious under 35 U.S.C 103).”
To provide adequate written description and evidence of possession of a genus of chemical compounds, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the claim is a reference to a partial structure in the form of a recitation of a “fragment.” There is not even identification of any particular portion of the structure that must be conserved. Moreover, it is not even clear what region of the FMRP polypeptide has the disclosed clinical significance. The specification does not provide a complete structure of those fragments that are suitable for administration to treat diseases associated with an increase in a DYRK1A and/or APP polypeptide in a subject and fails to provide a representative number of species for the recited genus. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the recited genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of the fragments, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
17. Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 are further rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating Fragile X syndrome by administration of an expression vector comprising a polynucleotide encoding a Fragile X mental retardation protein (FMRP), does not reasonably provide enablement for the full scope of the invention. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claims 1, 2, 4, 5, 10, 12, 13, 22, 24 and 26 are directed to methods of administration of FMPR polypeptide, or polynucleotide, or fragments thereof to reduce the level of Dual Specificity Tyrosine Phosphorylation Regulated Kinase 1 (DYRK1A) and/or amyloid-beta precursor protein (APP) in the cells of a subject with a developmental disorder or a neurodegenerative disorder and so to treat the disorder. However, the specification does not provide sufficient guidance to enable practice the full scope of the claimed invention without undue experimentation.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The specification discloses the invention as “the discovery that increasing the level of FMRP is sufficient to significantly reduce protein expression levels of APP and DYRK1A,
excess levels of which are associated with neurodevelopmental (e.g., Fragile X syndrome (FXS) or Downs syndrome) and/or neurodegenerative disorders (e.g., Alzheimer's disease
(AD)) by increasing expression of Fragile X Mental Retardation Protein (FMRP) in patients
having such disorders,” p. 41. It is further explained that, “[A]nalyses of multiple FXS and DS patient cell lines revealed a set of shared transcriptional and proteomic perturbations. Moreover, protein expression levels of two key HSA21-encoded FMRP targets, DYRK1A and APP, in DS patient cells were significantly reduced by acutely upregulating endogenous FMRP through CRISPRa. Collectively, these results support a novel model in which the loss of FMRP in FXS and an extra copy of HSA21 in DS converge on a set of shared gene targets through different mechanisms (i.e., through loss of an RNA binding protein and an extra copy of a chromosome, respectively)” p. 43. The working Examples at pp. 60-97 were performed using human pluripotent stem lines (hPSC), cultures of excitatory cortical neurons and specifically generated DS and FXS patient cell lines. The data indicate that FXR1P is a critical co-factor for majority of FMRP binding events in neurons, p.73; that FMRP targets are enriched for genes independently implicated in neurodevelopmental diseases, and further “that FMPR targets are enriched for genes transcribed from HSA21, [which] provides a potential molecular link between FXS and DS,” pp, 74-75. At Example 6, p. 79, the results of the experiments using a DS patient iPSC provided “proof-of-concept that transiently increasing endogenous FMRP in the context of DS is sufficient to significantly modulate key HSA21-encoded targets.” Finally, at pp. 81-85, Examples 7 and 8 explain the data as demonstration that upregulation of FMRP is sufficient to downregulate the expression of DS-implicated genes and to reverse one-fifth of the global transcriptional perturbation in DS. The specification provides no further information to support protocols of clinical administration of FMRP polynucleotide, or polypeptide, or fragments thereof, to reduce the levels of DYRK1A and/or APP for an effective therapeutic benefit to treat neurodevelopmental and neurodegenerative diseases, as currently claimed.
The nature of the invention places it in the class of invention which the Federal Circuit has characterized as "the unpredictable arts such as chemistry and biology." Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001).
The prior art recognizes treatment of Fragile X syndrome by administration of a vector comprising AAV and a polynucleotide encoding FMRP, see section 18 below. However, finding of FMRP as being associated with developmental and neurodegenerative disorders in general has not been reported. It is also not recognized in the art that reducing the level of DYRK1A and/or APP produces general positive clinical effect for developmental and neurodegenerative disorders.
With respect to claim breadth, the standard under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the enablement scope of the claims, the teachings of the specification are to be taken into account because the claims are to be given their broadest reasonable interpretation that is consistent with the specification (see MPEP 2111 [R-1], which states that claims must be given their broadest reasonable interpretation “During patent examination, the pending claims must be "given *>their< broadest reasonable interpretation consistent with the specification." In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).”
As such, the broadest reasonable interpretation of the claimed method is that it allows treatment of any developmental or neurodegenerative disorder by administration of FMPR polypeptide, or polynucleotide, or fragments thereof, and is not particularly limited to specific disorders only. Thus, the claims encompass an unreasonable number of pathological conditions of substantial phenotypic, pathophysiological, epidemiological and etiological heterogeneity, which the skilled artisan would not know how to evaluate.
Applicant has left those skilled in the art with too much experimentation to research and discover for themselves the effect, if any, of administration of a vector encoding FMRP, or FMRP polypeptide, or their fragments to a patient suffering from a developmental or neurodegenerative disorder. The art does not teach that FMRP, DYRK1A and/or APP are directly associated with every type of developmental or neurodegenerative disorder. The specification does not teach how to make decisions about the effective doses, or specific routes and regimes of administration, or how to determine when a compound is actually targeting the specific pathological marks. As such, Applicant has merely provided a starting point for research and experimentation and not a meaningful enabling disclosure of how to practice the claimed invention. Therefore, the claimed method of treatment—administration of a vector encoding FMRP, or FMRP polypeptide, or their fragments to broadly treat any developmental or neurodegenerative disorder—clearly lacks enablement, as disclosed.
A mere wish or plan of obtaining the claimed invention is not sufficient. The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure.” The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art,” “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.”
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution to perfect the method and complete the invention.
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.
18. Claim(s) 1, 2, 4, 5, 10, 12, 13 and 26 is/are rejected under 35 U.S.C. 102(a) as being anticipated by WO 2019/227219, 2019, document, reference 1 of IDS filed on 09/23/2022, the ‘219 document hence forth.
Claims 1, 2, 4 and 5 are broadly drawn to a method of contacting a cell comprising an increased level of a DYRK1A and/or APP, wherein the increased level is associated with Fragile X syndrome, with an expression vector comprising a polynucleotide encoding Fragile X mental retardation protein (FMRP). The ‘219 document teaches treatment of Fragile X syndrome by administration of an AAV-FMRP vector, see abstract, [0010], claim 19 and the whole text of the document. Thus, the step of administration of FMRP vector provides for a contact with the cells, such as any cell, within the body of the subject under treatment.
The ‘219 document does not teach increased levels of DYRK1A and/or APP in the cells of those with Fragile X syndrome, or that administration of FMRP vector results in reducing the level of the DYRK1A and/or APP in the cells. However, as explained earlier, see section 13 above, because the specification does not provide a clear definition of the term “associated with the developmental disorder or neurodegenerative disease,” by broadest reasonable interpretation the cells of a subject suffering from Fragile X syndrome fully meet the limitation as being “associated with the […] disease.” Thus, the act of contacting these cells with AAV-FMPR vector, as described by the cited art, produces the decrease in the level of DYRK1A and/or APP in the cells, absent evidence to the contrary.
Next, claims10, 12, 13 and 26 encompass a method of treating Fragile X syndrome by administration of FMRP polynucleotide. The ‘219 document teaches treatment of Fragile X syndrome by administration of an AAV-FMRP vector, see abstract, [0010], claim 19 and the whole text of the document. Thus, the ‘219 fully anticipates the instant claimed invention.
Conclusion
19. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA N CHERNYSHEV whose telephone number is (571)272-0870. The examiner can normally be reached 9AM to 5:30PM, Monday to Friday.
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/OLGA N CHERNYSHEV/Primary Examiner, Art Unit 1675
January 14, 2026