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 .
Claim Status
Claims 14-24 are pending. Claims 21-24 are newly added, and claims 14-20 were amended in the Reply filed 12/01/2025. As amended, claims 17-18 and 21 are withdrawn as directed to a non-elected species. Claims 14-16, 19-20, and 22-24 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group II (original claims 14-20) and the species of Example 6 (see, e.g., Spec. filed 6/16/2022 at 34 at line 25 to p. 36 at line 23) wherein a prophylactic dosage of 0.35 mg/kg of Paxilline was given to Ube3am-/p+ mice via intraperitoneal injection in the reply filed on 6/11/2025 is acknowledged.
The originally elected species is understood to be limited to a method of pre-treatment prior to injection with a GABAAR antagonist, and specifically is understood to be the species of Example 6 wherein a prophylactic dosage of 0.35 mg/kg of Paxilline was given to Ube3am-/p+ mice via intraperitoneal injection (see, e.g., Spec. filed 6/16/2022 at 34 at line 25 to p. 36 at line 23).
Following extensive search and consideration, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 14-16 and 19-24 are understood to continue reading upon the originally elected species in view of the amendments filed 12/01/2025. However, claims 17-18 and 21 were amended to exclude Paxilline, and therefore do not read upon the originally elected species.
Claims 17-18 and 21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6/11/2025.
During the search and examination of the originally elected species, art pertinent to other non-elected species was incidentally discovered. Although examination has not been extended beyond the non-elected species identified above per MPEP § 803.02, as a courtesy to the Applicant, this art has been applied below.
Claims 14-16, 19-20, and 22-24 are presently considered.
Priority
The priority claim to US Provisional 62/949603 (filed 12/18/2019) is acknowledged.
Information Disclosure Statement
No additional IDS was filed on 12/01/2025.
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Amended claim 14 is representative of the pending claim scope and presently recites:
14. (Original) A method of prophylaxis or treatment of seizures caused by one or more ubiquitin protein ligase E3A (UBE3A) mutations in a subject, comprising administering to the[[a]] subject a therapeutically effective amount of a compound or composition comprising an antagonist of Big Potassium (BK) channel activity, wherein the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity, and wherein the antagonist reduces said increased BK channel activity.
Accordingly, the claims are directed to methods of administering a compound to a patient population. The applicable claim interpretation is discussed below.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Applicable patient population: As amended, claim 14 no longer limits the claim scope to subjects “in need thereof”. Accordingly, the patient population is understood to subjects having (or at risk of having) “seizures caused by one or more UBE3A mutations in a subject”. Claim 14 is understood to be satisfied by any patient having “Angelman syndrome” or otherwise any “related autism spectrum disorder caused by loss or reduction of UBE3A” per dependent claim 16. Accordingly, the Applicable patient population includes at least patients known to have Angelman syndrome or “a related autism spectrum disorder caused by loss or reduction of UBE3A”.
Preamble: Regarding the preamble of claim 14, per MPEP § 2111.02, “where a patentee defines a structurally complete invention in the claim body and uses the preamble only to state a purpose or intended use for the invention, the preamble is not a claim limitation”. Here, the body of claim 14 is understood to recite a structurally complete invention, and therefore the preamble is deemed fully satisfied by prior art that satisfies the steps and structures recited in the body of the claim (see also MPEP § 2111.04(I), noting that “Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure”). Accordingly, the preamble is limiting only to the extent that it identifies the applicable patient population.
The “wherein” clause at amended claim 14 is understood to be fully satisfied by the originally elected species, using paxilline.
At claim 16, the phrase “caused by loss or reduction of function of UBE3A” is understood to modify “a related autism spectrum disorder”. Accordingly, claim 16 limits the patient population to patients having (i) Angelman syndrome and (ii) a related autism spectrum disorder caused by loss or reduction of function of UBE3A.
“BK Channelopathy” is understood to be satisfied by at least Angelman syndrome (see, e.g., Spec filed 6/16/2022 at 14 at lines 10-20).
Additional claim interpretations are set forth below.
Withdrawn Claim Rejections
The rejections of claims 14-20 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite, are withdrawn in part in view of Applicant’s amendments filed 12/01/2025. A revised rejection is set forth below.
The rejection of claim 17 on the basis that it contains an improper Markush grouping of alternatives (See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984)) is withdrawn in view of the amendments to claim 17.
The rejection of claims 14-18 and 20 under 35 U.S.C. 103 as being unpatentable over US 20090247607 A1 is withdrawn in view of the amendments to claims 15, 17-18, and 20. A revised rejection is set forth below.
The rejection of claims 14-20 under 35 U.S.C. 103 as being unpatentable over WO2017/075222 (May, 4, 2017) and further in view of Pelc1 and Sheehan2 is overcome, in part, by the amendments filed 12/01/2025. A revised rejection is set forth below.
Revised rejections under 35 USC 112(a) are set forth below.
New or Revised Claim Rejections Necessitated by Applicant Amendment
Claim Rejections - 35 USC § 112(b)
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.
Claims 14-16, 19-20, and 23 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.
Claim 14 requires a compound defined by reference to the functionally defined genus of “an antagonist of Big Potassium (BK) channel activity”, which renders the claim scope indefinite. Per MPEP § 2173.05(g),
..the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008)
Here, the phrase “an antagonist of Big Potassium (BK) channel activity” refers to a genus of unknown size and unknown structures defined only by reference to the function that Applicant hopes and desires the structures to achieve; however, the functional definition does not actually correspond to a structure/function relationship of record or otherwise known in the prior art. Therefore, an artisan would not be reasonably apprised of the metes and bounds of what structures do or do not constitute “an antagonist of Big Potassium (BK) channel activity”. Per MPEP § 2173, 35 USC § 112(b) is intended to ensure the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. Here, the claim is indefinite because an artisan would not reasonably be aware of what structures did or did not constitute “an antagonist of BK channel activity” in the absence of first testing and infringing. Accordingly, claim 14 is rejected as indefinite.
Amended claims 14 and 22 recite a patient population defined by a condition “in a subject”, wherein the condition is “seizures caused by one or more [UBE3A] mutations in a subject”, wherein “the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity”, which renders the claim scope indefinite. Per MPEP § 2173.05(g),
..the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. Halliburton Energy Servs., Inc. v. M-I LLC, 514 F.3d 1244, 1255, 85 USPQ2d 1654, 1663 (Fed. Cir. 2008)
Here, the patient population is functionally defined and limited only to conditions (i) having seizures caused by one or more UBE3A mutations, and more specifically (ii) only mutations that result in loss or reduction of UBE2A function, and more specifically (iii) only mutations that resulting in “increased BK channel activity”. This raises multiple indefiniteness issues that may be illustrated by the following threshold questions, which are not addressed in the originally filed disclosure or known in the art: (A) “Which exact mutations in UBE3A actually result in “increased BK channel activity’?” (B) “What exact ‘activity’ of a BK Channel is being ‘increased’?” (C) “What specific diseases and disorders are included or excluded by this functionally defined patient population?”. Regarding (A), the UBE3A gene would be understood by artisans to exceed 5000 nucleotides in length, and no guidance regarding SNPs, deletions, insertions, or other mutations that result in a “loss or reduction” of an unspecified function of UBE3A that “causes increased BK channel activity” is provided on record. Regarding (B), no clarification of what “activity” of the BK channel is “increased” is recited in a definition of a structure/function relationship of record. This is pertinent because the BK channel has multiple functions and may be characterized in multiple ways using biochemical analysis. For example, ion-channel conductance, BK channel ubiquitination and proteasomal degradation mediated by UBE3A, BK Channel expression levels (i.e., mRNA transcript production), BK Channel protein expression (i.e., mRNA translation rate), BK Channel binding, BK Channel trafficking, etc., etc. Accordingly, presumably, the claim encompasses “increased” activity regarding any aspect of the BK Channel. Regarding (C), in the absence of clarification of what exact mutation of UBE3A result in both “loss or reduction of UBE3A function” and also “increased BK Channel activity” (wherein the specific ‘function’ and ‘activity’ are not specified), and artisan would not reasonably be apprised of what specific diseases, disorders, or conditions could actually be treated with the claimed method (i.e., the patient population is indefinite in view of the functional definition that fails to correspond to any structure/function relationship). For example, what specific “autism spectrum disorders” are included or excluded from the scope of claims 12 and 22? Is Asperger’s Syndrome included or excluded? Is PDD-NOS included or excluded? Is CDD included or excluded? Is Rett Syndrome included or excluded? Are all Angelman Syndrome patients included, or are a subpopulation excluded? 3 In sum, the amended claim merely recites a functionally defined patient population by reference to functionally defined UBE3A mutations that achieve a functionally defined outcome, and this nesting of multiple functionally defined terms and phrases fails to meaningfully correspond to a particular patient population. Even assuming arguendo that screening techniques could be performed for particular UBE3A mutations, this would be insufficient to identify the claimed patient population because it is unknown what mutations (from among thousands of possible mutations) actual satisfy the subsequently recited functional limitations. Per MPEP § 2173, 35 USC § 112(b) is intended to ensure the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. Here, an artisan would not reasonably be aware of what patient population (i.e., specific UBE3A mutations) were included or excluded by the pending claim scope without brute-force testing and potentially repeatedly infringing upon the claim scope. Accordingly, the claim scope is indefinite per MPEP § 2173.05(g). For purposes of applying prior art, claims 14 and 22 are understood to read upon any patient diagnosed with Angelman Syndrome. Applicant could overcome this rejection by amending the claim scope to remove the functional language, and simply recite a method of “treating patients having Angelman Syndrome”.
Claim 16 is rejected for recitation of “a related autism spectrum disorder caused by loss or reduction of UBE3A”. First, the term “related” is a relative term which renders the claim indefinite. First, the term “related” is 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 (i.e., the question “related to what?” is left unaddressed). For example, it is unclear if all injuries that may occur in patients with autism constitute “related autism spectrum disorder” or not (e.g., broken leg, upset stomach, etc.) if “related” to autism or having an “autism spectrum disorder”. Second, the amended portion of claim 16 now stipulates that the “related autism spectrum disorder” is limited to an unknown subgenus of “related autism spectrum disorders”, namely only the ones “caused by loss or reduction of UBE3A” (see claim 16). At no point in the originally filed disclosure is there a corresponding structure/function relationship, discussion of “related autism spectrum disorders” that are or are not “caused by loss or reduction of UBE3A”, or any guidance reasonably informing an artisan of what disorders are included or excluded by this functional limitation. Identification of the metes and bounds of this subgenus defined by reference to “causation” requires a complete understanding of (i) all possible cases of any “related autism spectrum disorder”, and (ii) the specific underlying mechanistic aspects and biochemical pathways through which these unspecified “related autism spectrum disorders” may be “caused by” loss or reduction of UBE3A (i.e., SNPs, silent mutations, deletions, insertions, UTR truncations, rearrangements, binding kinetics, etc.). However, no corresponding structure/function relationship is on record or otherwise known in the art reasonably identifying the metes and bounds of what subjects are included or excluded by the phrase “a related autism spectrum disorder caused by loss or reduction of UBE3A”. In fact, the Specification informs artisans that the understanding of the underlying mechanistic aspects and biochemical pathways involving UBE3A was actually incomplete4. Accordingly, an artisan would not realistically know how to differentiate between patients having “a related autism spectrum disorder”, and the narrower subpopulation of patients having such conditions specifically “caused by loss or reduction of function of UBE3A” as now claimed. Per MPEP § 2173.05(g),
..the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971).
Accordingly, the functionally defined patient population renders the claim scope indefinite because it is unknown how to differentiate the previously claimed population of all possible subjects having some unknown “related autism spectrum disorder” and the narrower subpopulation of such unknown patients that have the unspecified “related” conditions specifically “caused by loss or reduction of function of UBE3A”. In addition or alternatively, what a condition is deemed to be “caused by” or not “caused by” may change over time as research advances and provides more clarity, and therefore the patient population “in need of” such treatment as instantly claimed necessarily varies as the scientific understanding of causation varies over time (see, e.g., MPEP § 2173.05(b)(II), explaining that a claim may be rendered indefinite when a limitation of the claim is defined by reference to a variable object and the relationship is not sufficiently defined). Accordingly, the claim is indefinite. In sum, the reference to underlying “causation” requires knowledge of a structure/function relationship is that not known or provided on record, and therefore it is unclear how to meaningfully differentiate what patients are included or excluded by statements requiring causation. For purposes of applying prior art, the patient population at claims 14 and 16 are understood to at least read upon any patients diagnosed with Angelman syndrome.
Amended claim 19 recites “wherein the antagonist is a small-molecule BK channel inhibitor”, which renders the claim indefinite because it is unclear what small-molecules do or do not satisfy the functional limitation. One of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Per MPEP § 2173.05(g),
..the use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. . . .
Here, the claim defines a genus of unspecified small-molecule structures by a desired activity that Applicant hopes to achieve, rather than by a common structure actually capable of achieving that activity. Zero structure/function relationships are set forth on record defining any common, shared structural motifs defining a genus of “small-molecule BK channel inhibitors”. Rather, the disclosure, at best, teaches two small molecules (Paxilline and GAL-021), which appear to not share any appreciable common structural motif responsible for “BK channel inhibitor” functionality (see, e.g., Spec. at 3-4). Accordingly, the functionally defined subgenus fails to correspond to a clear structure/function relationship of record, and therefore an artisan would not be aware of what structures were included or excluded by the functionally defined genus in the absence of infringing (i.e., brute force testing). The courts have stated
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Notably, per MPEP § 2173, 35 USC § 112(b) is intended to ensure the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. Here, an artisan would not reasonably be aware of what structures did or did not constitute “BK channel inhibitor” prior to testing and potentially infringing. Accordingly, claim 19 is rejected as indefinite. For purposes of applying prior art, amended claim 19 is understood to read upon the originally elected species.
Claims 15-16, 19-20, and 23 depend directly or indirectly from a rejected base claim and fail to clarify the indefiniteness of the base claim. Accordingly, claims 15-16, 19-20, and 22-24 are also rejected as indefinite for the reasons applicable to instant claim 14.
Claims 14-16, 19-20, and 23 are rejected.
Claim Rejections - 35 USC § 112(a), Written Description
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.
Claims 14-16, 19-20, and 22-24 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.
Brief Statement of the Issue(s)
The pending claims recite methods of using a functionally defined genus of unspecified compounds (i.e., “an antagonist of BK channel activity”), which may comprise trillions of compounds or perhaps less than a dozen, to treat or prevent a functionally defined genus of seizures (i.e., “seizures caused by one or more UBE3A mutations . . . wherein the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity”) by administering (via any route of administration) a functionally defined “effective amount” of the unspecified compound.
Claim Scope
Amended claim 14 and newly added claim 22 are representative of the pending claims scope.
The applicable claim interpretations have been set forth above under 35 USC 112(b) and in a separate claim interpretation section. Those discussions are incorporated herein.
It is unclear if the claimed methods encompass trillions of species of treating or preventing seizures via all forms of administration (e.g., topical, anal, oral, intramuscular, intravenous, etc.) using any functionally described compounds (i.e., “an antagonist of BK channel activity”), or if the claim scope only reads upon the treatment of patients with Angelman syndrome or an Autism Spectrum Disorder by administering two or three compounds (i.e., iberiotoxin, paxilline, GAL-021). Accordingly, the claim scope appears to be vast and highly varied.
Actual Reduction to Practice
One embodiment of the claimed invention was reduced to practice wherein a single compound was administered to a subject, namely the originally elected species of Example 6 (see, e.g., Spec. filed 6/16/2022 at 34-36 at § Example 6). The disclosed embodiment tests a single compound (Paxilline) in a single animal model (i.e., Ube3am-/p+ mice) via a single administration route (i.e., intraperitoneal (i.p.)) at 0.35 mg/kg-10 mg/kg (see, e.g., Spec. filed 6/16/2022 at 34-36 at § Example 6)
Assessment of whether disclosed species are representative of the claimed genus
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus (see, e.g., MPEP § 2163(II)(3)(a), MPEP §2163.03(V)). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
In this case, the claims encompass an essentially infinite number of methods of treating a vast number of subjects by administering compounds selected from a presumably vast genus of functionally defined compounds, via any administration route, at an unspecified and functionally defined concentration identified as “a therapeutically effective amount”. Accordingly, there is substantial variation within the claimed genus.
The single example fails to reflect the variation within the genus because it pertains to a single model system, single route of administration, single small molecule compound5, and critically, the single example actually informs artisans that the sole embodiment reduced to practice shows that the tested compound only works as intended at concentrations at 0.35 mg/kg to under 3 mg/kg because 3 mg/kg “resulted in increased seizure susceptibility in WT mice”, and “10 mg/kg paxilline caused seizures in WT and KO mice” (see, e.g., Spec. filed 6/16/2022 at 36 at lines 10-25). Accordingly, zero “therapeutically effective” amounts above 3 mg/kg for paxilline (or any compound) was actually objectively identified on record (see id).
Zero examples of non-mouse subjects were tested and reduced to practice.
Zero examples of small molecules other than Paxilline were shown to reduce or prevent seizures at any dosage, any model, via any route of administration.
Zero examples of methods of administering to subjects any other compounds such as IBTX, GAL021, or “functional nucleic acids” (e.g., antisense, aptamers, ribozymes, triplex forming molecules, siRNA, RNAi, EGS, etc.) were reduced to practice at any concentration or via any administration route.
Zero “therapeutically effective” amounts above 3 mg/kg for paxilline (or any compound) was actually objectively identified on record in subjects for preventing or treating seizures in subjects with one or more UBE3A mutations.
Although the MPEP does not define what constitutes a sufficient number of representative species, the Courts have indicated that the disclosure of two species within a subgenus did not describe that subgenus. In re Gostelli, 872 F.2d at 1012, 10 USPQ2d at 1618. Similarly, the disclosure of the single example of Example 6 does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus. Similarly, the disclosure of zero examples of non-Paxilline based treatments using nucleic acids or other small molecules in any non-mouse subject at any safe dosage outside the range of 0.35-3 mg/kg, via any non-i.p. route of administration, does not provide sufficient disclosure to satisfy the written description requirement for the instantly claimed genus.
Identifying characteristics of the genus
In the absence of a reduction to practice of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
An initial question is simply “what does or does not constitute ‘an antagonist of BK channel activity’ as required to practice the claimed method?” Although the originally filed disclosure exemplifies generic classes of structures (see, e.g., originally examined claim 17, referring to “small molecules”, “aptamers”, “siRNA”, etc.) and experimental evidence using Paxilline, the metes and bounds of what exact structures are included or excluded by this functional limitation is unknown (see rejection under 35 USC §112(b), above; incorporated herein). This is relevant because the courts have stated
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, the inability to differentiate what does or does not constitute “an antagonist of BK channel activity” weighs in favor of a determination that the disclosure does not satisfy the written description requirements of 35 USC § 112(a).
Another basic threshold question is “what patient population is being defined by reference to ‘seizures caused by one or more UBE3A mutations . . . wherein the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity’?”. At best, from amended, dependent claim 16, this phrase is satisfied by subjects having Angelman Syndrome, but the full scope of the claim is unknown since claims 14 and 16 read upon all subjects having any “related autism spectrum disorder caused by loss or reduction of UBE3A”. This subgenus is undefined on record and undefined in the art, and therefore it is unknown what “disorders” are “related” and do or do not fall within the scope of instant claims 14 and 16. Regarding amended claim 14, the claimed invention requires that an artisan be able to differentiate among patient populations based upon “causation” at a molecular level, which appears to require an unclaimed screening step; however, no such “screening step” for all disorders “caused by” UBE3A mutations is actually disclosed on record or known in the prior art.
Regarding patient population and “causation”, no disclosure regarding a reasonably complete understanding of the underlying mechanistic aspects and biochemical pathways through which UBE3A mutations cause seizures either directly or indirectly (i.e., SNPs, silent mutations, deletions, insertions, UTR truncations, rearrangements, etc.) is provided on record or known in the prior art. In fact, the Specification informs artisans that the understanding of the underlying mechanistic aspects and biochemical pathways involving UBE3A was incomplete6. Accordingly, an artisan would not realistically know how to differentiate between seizures “caused by” such mutations and “seizures” not caused by such mutations. Accordingly, the written description is insufficient to permit artisans to unambiguously identify the intended patient population from an unintended patient population.
It is the Examiner’s understanding that Applicant is alleging that the patient populations defined by a condition “in a subject”, wherein the condition is “seizures caused by one or more [UBE3A] mutations in a subject”, wherein “the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity” (claims 14 and 22). However, the only “mutation” tested was KO mice using paxilline (see, e.g., Spec. filed 6/16/2022 at 36 at lines 10-25). This is pertinent because the proffered data at Example 6 is limited to UBE3A KO mice (mice with maternal Ube3a deletion) (see, e.g., Spec. filed 6/16/2022 at 34-36 at § Example 6), which does not meaningfully place the Applicant in possession of any single “mutations” at any particular position or domain within UBE3A (i.e., the mRNA transcript for UBE3A is over 5000 nucleotides in length) that actually “result in loss or reduction of UBE3A function that causes increased BK channel activity”. For example, if the protein of UBE3A is mutated (i.e., deleted, altered by insertion, substituted) at position X, wherein X can be any position within the UBE3A protein, it is unclear if that mutation actually “results in loss or reduction of UBE3A function that causes increased BK channel activity”. Although such information is discoverable using screening methods and brute-force testing, the possession of an idea for screening is not equivalent to possession of a specific subset of UBE3A mutations actually required to identify the patient population encompassed by the instant claims. Rather, the courts have explained that the description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Furthermore, the courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). Here, the functional language relied upon is equivalent to “merely drawing a fence around a perceived genus”, while “leaving it to others to explore the unknown contours of the claimed genus”, since the disclosure fails to actually identify what specific structures qualify as “antagonists” as claimed.
One substantial and material concern raised by the originally filed disclosure is “what does or does not constitute a ‘therapeutically effective amount’ of an unspecified compound administered via an unspecified route of administration to an unspecified patient population?” At best the originally filed disclosure provides vague and generic guidance regarding what they hope and desire constitutes an “effective amount” (see, e.g., Spec. filed 5/16/2022 at 5 at lines 1-5 and 20-25, original claim 20). However, this disclosure is subsequently contradicted by a disclosure identifying that the only compound actually tested on record (i.e., Paxilline) in the claimed method actually causes seizures at concentrations within the disclosed and claimed ranges (see, e.g., Spec. filed 5/16/2022 at 36 at lines 10-24, noting that “10 mg/kg paxilline caused seizures in WT and KO mice” and that “3 mg/kg . . . increases seizure susceptibility”; note that amended claim 14-16, 19, and 22-24 continue to read upon unbounded concentration ranges). Accordingly, this evidence of lack of enablement at concentrations near and overlapping with the claimed and disclosed concentration ranges raises a substantial and material concern regarding what does or does not constitute a “therapeutically effective amount” of Paxilline in subjects other than the tested Ube3am-/p+ mice, and what does or does not constitute a “therapeutically effective amount” of siRNA, IBTX, GAL021, aptamers, antisense molecules (LNAs, PNAs, MOEs, etc.), unspecified small molecules, and other compounds that constitute “an antagonist of BK channel activity” (proteins, antibodies, etc.?). Accordingly, generic guidance amounting to concentration ranges the Applicant hopes will achieve desired results combined with evidence that such ranges do not even prevent seizures in the single example reduced to practice, create substantial and material confusion regarding what does or does not constitute an “effective amount” of any compounds that constitute “an antagonist of BK channel activity” as presently claimed. Therefore, the written description is insufficient to permit artisans to unambiguously and meaningfully identify what concentrations do or do not constitute “therapeutically effective amounts” in the full range of subjects or for any particular compound that constitutes “an antagonist of BK channel activity” as presently claimed.
Accordingly, basic identifying characteristics pertinent to the claimed genus are left unanswered as explained above. Therefore, the guidance set forth in the originally filed disclosure is insufficient to permit an artisan to meaningfully identify the structures, steps, concentrations, and patient populations included or excluded by the pending claim scope.
Predictability in the Art
Although the level of skill in the art is high, the predictability in the clinical arts is low due to the complexity of biological systems, differences in patient populations, differences between compounds having different structures and different mechanisms of action, concentration effects, administration route effects, dosage frequency effects, and “causation” of seizures. Specifically, an artisan would not be able to predict or identify, a priori, and in the absence of any guidance, the minimal, common structures, and “therapeutically effective” concentrations, of all possible compounds that are capable of successfully “treating” seizures “caused by” mutations in UBE3A, including compounds having distinct underlying mechanisms of action (e.g., siRNA vs PNA vs small molecule vs antibody).
Accordingly, in the absence of sufficient structure/function teachings identifying what does or does not constitute a “therapeutically effective amount” of any particular compound for the successful treatment of patients having or at risk of having seizures specifically “caused by one or more UBE3A mutations”, via any route of administration, as required by the pending claims, an artisan would not reasonably conclude that Applicant possessed the full scope of the broad and highly varied genus of methods recited and encompassed by the instant claims.
Conclusion
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). The courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). In addition, the Courts have stated
“[r]egardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
This is pertinent because, in the instant case, Applicants have claimed a broad and highly varied genus of methods comprising an unknown number of ill-defined compound defined by reference to functional limitations; however, the originally filed disclosure has failed to identify any common structure/function relationship sufficient to permit an artisan to identify what structures are included or excluded by the claim scope. This also means that it is prima facie unclear what structures are infringe or do not infringe upon the pending claim scope.
The courts have held that a claim to a therapeutic method requiring administration of an “effective” amount of a compound at specific dosage range set forth in the disclosure for the treatment of a broad array of disorders failed to satisfy the Written Description Requirement because the disclosure addressed only “basic research and broad []dosage ranges”, but did not establish possession of a “therapeutically effective [] dose at the time of filing” (see, e.g., Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *8 (Fed. Cir. 2021). The court clarified that although
An inventor need not "prove that a claimed pharmaceutical compound actually achieves a certain result. But when the inventor expressly claims that result, our case law provides that [such] result must be supported by adequate disclosure in the specification.”
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343 (Fed. Cir. 2021).
The court further explained that
That Biogen later established the therapeutic efficacy of [a known compound at a specific dosage] is of no import to the written-description analysis. What matters for purposes of the inquiry [*1344] in this case is whether, at the time of filing the disclosure—well before the Phase III study even commenced—a skilled artisan could deduce simply from reading the specification that [a known compound at a specific dosage] would be a therapeutically effective treatment for MS. As to this point, the specification's focus on drug discovery and basic research further buttresses the district court's conclusion that the specification lacks an adequate written description to support the [] claims. . . . the law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d at 1353 . The written-description requirement limits patent protection only to individuals who perform the difficult work of producing a complete and final invention featuring all its claimed limitations and publicly disclose the fruits of that effort.
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1344, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *9 (Fed. Cir. 2021); emphasis added
Here, like in Biogen, the Specification is directed to basic research without clear clinical data sharing a nexus with the claims because a single embodiment of the claimed invention was actually reduced to practice, but zero variability in patient populations, compound variation, variation in route of administration, or compound-specific “effective amounts” were discussed with specificity. Furthermore, unlike Biogen, here the claims further attempt to draw a fence around the treatment of all possible species of “seizures caused by one or more UBE3A mutations in [any] subject” using any possible (but unspecified) “antagonist of BK channel activity” at any possible (but unspecified) “therapeutically effective amount” via any possible (but unspecified) route of administration. Therefore, the instant claims are substantially broader in scope than the claims of Biogen, but the disclosure of the instant Specification appears to provide substantially less guidance than that of the specification at issue in Biogen. Therefore, like Biogen, the instant claims lack written description support because an artisan “simply from reading the specification” could not deduce which compound at what concentration any particular “antagonist of BK channel activity” would be “effective” for any particular “seizures caused by one or more UBE3A mutations in [any] subject”, as presently claimed.
In conclusion, for the reasons discussed above, the skilled artisan would not reasonably conclude that the inventor(s), at the time the application was filed, had possession of the full scope of the claimed invention.
Claims 14-16, 19-20, and 23 are rejected are rejected
Claim Rejections - 35 USC § 112(a), New Matter
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.
Claims 16 is 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.
Applicable Case Law
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Lack of literal Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163.
Claim 16 recites “a related autism spectrum disorder caused by loss or reduction of function of UBE3A”, which is a functionally defined subgenus of “related autism spectrum disorders” which does not literally appear in the originally filed disclosure.
Lack of Implicit or Inherent Support
The MPEP states that "[w]hile there is no in haec verba requirment, newly added claim limitations must be supported in the specification through express, implicit, or inherent disclosure." See MPEP 2163. As noted above, the claims are not literally or inherently supported by the originally filed disclosure. Accordingly, the relevant issue is whether or not the new amendments and resulting claim scope is implicitly or inherently supported by the originally filed disclosure.
The added phrase “caused by loss or reduction of function of UBE3A” is a functional limitation that fails to correspond to any known structure/function relationship on record or in the prior art. It is prima facie unknown what exact “related autism spectrum disorders” do or do not fall within the scope of “a related autism spectrum disorder caused by loss or reduction of function of UBE3A”, and zero literal, inherent, or implicit guidance is provided in the originally filed disclosure. Accordingly, the functionally-defined subgenus of disorders lacks implicit support on record.
Conclusion
Per MPEP § 2163, new or amended claims which introduce elements or limitations which are not supported by the as-filed disclosure violate the written description requirement (see, e.g., In re Lukach, 442 F.2d 967, 169 USPQ 795 (CCPA 1971)). Here, the newly added claim limitations result in a narrower claim genus which defines a novel subgenus of species that was not inherently, implicitly, or literally supported by the originally filed disclosure.
“A written description sufficient to satisfy the requirement of the law requires a statement of an invention, not an invitation to go on a hunting expedition” (see Indivior UK Ltd. v. Dr. Reddy’s Laboratories S.A., 18 F.4th 1323, 1329 (Fed. Cir. 2021).
Claim 16 is rejected.
Claim Rejections - 35 USC § 112(a), Scope of Enablement
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.
Claims 14-16, 19-20, and 22-24 are 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 methods of prophylaxis or treatment of seizures in subjects having Angleman syndrome by administering a prophylactic dosage of 0.35 mg/kg of Paxilline via intraperitoneal injection, does not reasonably provide enablement for prophylaxis or treatment of seizures in all subjects having any possible disease or disorder characterized by “one or more UBE3A mutations [that] result in loss or reduction of UBE3A function that causes increased BK channel activity” by administering “about 10 mg/kg” of Paxilline. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The applicable legal standards for enablement are discussed at MPEP § 2164 and the specific legal standards relevant to determinations regarding the scope of enablement are set forth at MPEP § 2164.08. MPEP § 2164 identifies the following relevant factors for determining “undue” experimentation: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.” The factors which have led the Examiner to conclude that the specification fails to teach how to make and/or use the claimed invention without undue experimentation, are addressed in detail below.
Claims 14 and 22 are representative of the pending claim scope, and the interpretation of claim 14 has been discussed in a separate claim interpretation section and preceding rejections, as set forth above. Those teachings are incorporated herein.
The pending claims are understood to encompass at least the treatment of seizures (see instant claims 14 and 22) in patients with Angelman syndrome (or animal models thereof) by administering to patients a pharmaceutically acceptable composition comprising Paxilline (see instant claims 17-19), wherein Paxilline is administered at an unbounded “therapeutically effective concentration” encompassing at least “about 0.05” to “about 10 mg/kg” (see original claim 20, Spec. filed 6/16/2022 at 5 at lines 3-5 and 20-25).
This is problematic because the originally filed disclosure teaches that Paxilline actually causes seizures in wildtype and Angelman syndrome animal models when administered at 10 mg/kg (see, e.g., Spec. filed 5/16/2022 at 36 at lines 10-24, noting that “10 mg/kg paxilline caused seizures in WT and KO mice” and that “3 mg/kg . . . increases seizure susceptibility”). Accordingly, the specification fails to provide any evidence that Applicant disclosed how to make and use a method of preventing or treating such seizures by administering Paxilline at such concentrations, because the specification literally discloses that concentrations of “about 10 mg/kg” “caused seizures” rather than preventing or treating them.
Therefore the instant disclosure sets forth evidence showing that the disclosure is not fully enabled because it literally teaches that higher doses of Paxilline cause seizures in the single experiment of record, and fails to disclose any working concentration of Paxilline (or any compound) capable of treating or preventing seizures at any concentration other than 0.35 mg/kg and 3 mg/kg (see, e.g., Spec. filed 5/16/2022 at 36 at lines 10-24).
The prior art provides no guidance regarding how inducing seizures can reasonably be deemed to treat or prevent seizures. Accordingly, an artisan would predict and expect that amounts of “about 10 mg/kg” of such substances would actually induce and cause seizures based on the evidence of record. No guidance is provided for any other compound besides Paxilline in vivo.
The quantity of experimentation required to practice the claimed invention based on the teachings of the specification. One of skill in the art would not reasonably conclude that seizures could be prevented or treated by inducing a seizure in view of the prior art. Furthermore, an artisan would not reasonably conclude that Paxilline (or any other compound within the scope of instant claim 14) could be successfully administered at a concentration of “about 10 mg/kg” or other than about 0.35 mg/kg to about 3 mg/kg. Accordingly, to practice the full scope of the instantly claimed invention an artisan would be unduly burdened to actually identify an “effective” dose, administration routes, patient populations, and compounds that actually resulted in the treatment or prevention of seizures as instantly claimed, at concentrations above 3 mg/kg, such as “about 10 mg/kg”. However, such work would constitute a novel discovery and no evidence of record suggests that such treatments are actually possible.
Conclusion: Therefore, in view of the lack of guidance and working examples, high degree of unpredictability, and failure to address the concerns present in the art, an artisan would be unduly burdened with experimentation in order to practice the full scope of the instantly claimed invention, because the full scope appears to be impossible to achieve in view of the proffered data in the originally filed specification.
Accordingly, claims 14-16, 19-20, and 22-24 are rejected are rejected.
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.
Claims 14, 16, and 23 are rejected under 35 U.S.C. 103 as being unpatentable over US 20090247607 A1 (cited in previous action).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Ubiquitin-protein ligase E3A (a.k.a., UBE3A) is also known in the art as E6AP ubiquitin-protein ligase (E6AP). Additional claim interpretations are set forth below.
Regarding instant claims 14 and 16, US’607 identifies that a “dsRNA targeting E6AP may be employed to treat neurological and behavioral disorder” and explicitly recites and exemplifies Angelman syndrome (see, e.g., US’607 at ¶[0131], emphasis added; compare id. within instant claims 14-16, noting that Angelman syndrome is a BK channelopathy). US’607 identifies that Angelman syndrome is characterized by seizures (see, e.g., US’607 at ¶[0131]), and therefore an artisan would readily appreciate that treating patients with Angelman syndrome by administering a dsRNA targeting E6AP would necessarily result in the “treatment” of symptoms associated with Angelman syndrome, including seizures (see, e.g., US’607 at ¶[0131]). Regarding claims 14 and “an antagonist of BK channel activity”, a dsRNA decreasing UBE3A would be “an antagonist of BK channel activity”, wherein the “activity” is BK channel ubiquitination and proteasomal degradation mediated by UBE3A, and wherein targeting UBE3A with dsRNA would antagonize this “activity”. Regarding instant claim 23, US’607 identifies that dsRNA may be formulated with pharmaceutically acceptable buffers (i.e., salts) and carriers. US’607 explicitly discloses that dsRNA may be administered at dosages “less than 5 mg/kg body weight of the recipient” (see, e.g., US’607 at ¶¶[0068], [0099]). US’607 identifies that dsRNAs can be administered via multiple routes of administration, including intraperitoneal injection (see, e.g., US’607 at ¶[0104]).
US’607 differs from the claimed invention as follows: US’607 does not reduced to practice a method wherein a dsRNA targeting UBE3A (i.e., E6AP) is administered to patients at less than 5 mg/kg via intraperitoneal injection to treat Angelman syndrome.
However, it is well-within the ordinary skill in the art to simply follow the teachings and guidance set forth in the prior art, and to administer dsRNA to patients with Angelman Syndrome at dosages “less than 5 mg/kg body weight” via intraperitoneal injection (see, e.g., US’607 at ¶¶[0068], [0099], [0104], [0131]7).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): It is obvious to combine known prior art elements according to known prior art methods to achieve the exact results taught and disclosed by the prior art (see, e.g., MPEP § 2143(I)(A), (G)). Here, it would be obvious to follow the guidance of US’607 and to treat a patient having Angelman Syndrome, and at risk for seizures, dsRNA at dosages of 5 mg/kg or less via intraperitoneal injection in order to predictably treat Angelman Syndrome and reduce associated side-effects of the syndrome, exactly as taught and suggested by the prior art. Furthermore, each prior art element merely performs is art-recognized function in combination as it does separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well within the ordinary skill in the art to administer a known compound to a known patient population at a known dosage using a known route of administration to achieve the exact, known outcome identified by the prior art reference.
Accordingly, claims 14, 16, and 23 are rejected.
Claims 14-16, 19-20, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over WO2017/075222 (May, 4, 2017) and further in view of Pelc8 and Sheehan9.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
WO’222 pertains to the treatment of neurological or neurodevelopmental diseases or disorders by administering antagonist of potassium (K) channel (see, e.g., WO’222 at title, abs). Regarding instant claims 14-16, 19-20, 22-24, and the general treatment of patients having neurological or neurodevelopmental diseases or disorders such as an autism spectrum disorder by administering Paxilline at 0.05 mg/kg to 10 mg/kg, WO’222 directs artisans to treat patients having autism and autism spectrum disorders “and the like” by administering to a patient in need thereof a therapeutically effective amount of an antagonist of potassium channels (see, e.g., WO’222 at title, abs, claims 1, 4, 11, 15, 17-18), wherein the antagonist of K channels may be Paxilline (see, e.g., WO’222 at ¶[0056]) at a therapeutically effective amount of “about 0.5 . . . mg/kg” or between 0.001 mg/kg and 10 mg/kg (see, e.g., WO’222 at ¶[0062]; see MPEP § 2144.05(I)10), delivered with a pharmaceutically acceptable carrier (see, e.g., WO’222 at ¶[0058]) via intraperitoneal injection or other administration routes (see, e.g., WO’222 at ¶[0059]). In sum, the prior art the prior art already directs and guides artisans to treat neurological or neurodevelopmental diseases or disorders by administering ~0.5 mg/kg of Paxilline via intraperitoneal injection.
The teachings of WO’222 differ from the instant claims as follows: WO’222 does not specifically mention the treatment of seizures associated with Angelman syndrome.
Pelc is cited herein to establish that Angelman syndrome is an art-recognized neurogenetic disorder and neurodevelopmental disorder caused by lack of proper UBE3A gene expression (see, e.g., Pelc at abs, 212 at col I at 1st ¶ to col II at 1st partial ¶, 215 at col I at 1st full ¶). Pelc identifies that Angelman syndrome is known to be associated with increased risk of epilepsy and seizures (see, e.g., Pelc at title, abs, 215 at col I-I at § “Management”). Pelc identifies that seizures in patients with Angelman syndrome are typically controlled by administering antiepileptic drugs to such patients (see, e.g., Pelc at 215 at col I-I at § “Management”).
Sheehan identifies that Paxilline was an art-recognized BK-channel antagonist that was reported as capable of treating seizures in animal models following intraperitoneal injection (see, e.g., Sheehan at title, abs). Sheehan identifies that they hypothesized that systemic administration of BK-channel antagonists (i.e., Paxilline) could treat or prevent propagation of epileptic activity in vivo (see, e.g., Sheehan at 716 at col II at 1st full ¶), and that “BK-channel antagonists hold therapeutic promise in the treatment of “seizure disorders” (see, e.g., Sheehan at 719 at col II at 1st partial ¶). Accordingly, an artisan would readily appreciate that BK-channel antagonists would be reasonably expected to be able to treat seizures upon systemic delivery, and therefore would be reasonably considered an antiepileptic drug.
In sum, the primary reference establishes that Paxilline would have already been administered to the same or overlapping patient population via the same administration route and at the same or overlapping concentration, in order to predictably treat any neurodevelopmental disorder known in the prior art (see discussion regarding WO’222, above), which, as established by Pelc, would include Angelman syndrome. Accordingly, Angelman syndrome would be reasonably inferred to be within the scope of WO’222. Furthermore, Angelman syndrome was known in the art to be associated with seizures, and Sheehan identifies that Paxilline would also desirably and beneficially be expected and predicted to treat seizures. Accordingly, following the guidance of the primary reference to treat the neurodevelopmental disorder of Angelman syndrome by administering Paxilline in the amounts taught by WO’222 would be predicted to desirably treat Angelman syndrome and to also desirably and expectedly treat seizures associated with Angelman syndrome.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the treatment of a neurodevelopmental disorder (i.e., Angelman syndrome) by administering the potassium channel inhibitor of Paxilline exactly as taught and suggested in view of the primary reference, wherein in view of Pelc and Sheehan, an artisan would readily predict and expect that administration of Paxilline to such patients would also advantageously treat or reduce seizures associated with the neurodevelopmental disorder (i.e., Angelman syndrome). Furthermore, each element was known in the prior art, and merely performs its art-recognized function in combination (see, e.g., MPEP § 2143(I)(A), (F), (G)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to treat a known patient population having a known neurodevelopmental disorder with a known compound at a known dosage and known route of administration, exactly as taught and suggested by the primary reference.
Accordingly, claims 14-16, 19-20, and 22-24 are rejected.
Response to Arguments
Applicant's arguments filed 12/01/2025 have been fully considered but they are not persuasive for the reasons discussed below.
35 USC 112(b)
It is the Examiner’s understanding that Applicant addresses the rejections under 35 USC 112(b) at pages 7-9 of the Reply (see, e.g., Reply filed 12/01/2025 at 7 at 1st full ¶ to 9 at 1st partial ¶). Arguments pertaining to withdrawn claims or withdrawn rationales not maintained above, are moot. Remaining applicable arguments have been fully considered, but not found persuasive for the reasons discussed below.
It is the Examiner’s understanding that Applicant is alleging that the phrase “an antagonist of Big Potassium (BK) channel activity” is not indefinite, and satisfies the requirements of 35 USC § 112(b) (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶ to 9 at 1st partial ¶). The applicable arguments are addressed below.
First, it is the Examiner’s understanding that Applicant alleges that the claims now recite “specific antagonists” (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶). This is only correct for amended claims 15, 17-18, 20, 22, and 24, which are not at rejected for this particular issue. However, claims 14, 16, 19, and 23 do not recite “specific antagonists”, and therefore such arguments do not apply to those claims. Accordingly, claims 14, 16, 19, and 23 are not limited to “specific antagonists”.
Second, it is the Examiner’s understanding that Applicant alleges that the functional limitations at claim 14 “ensures that the claimed method applies only to compounds or compositions that demonstrably correct the identified abnormality” (see, e.g., Reply filed 12/01/2025 at 7-8 at bridging ¶). This assertion is tautological in nature because it merely repeats the Applicant’s intent, basis, and desired claim scope pertaining to the functional language, but fails to actually identify any meaningful structure/function relationship of record that would clearly and precisely inform persons skilled in the art of the boundaries of protected subject matter in order to avoid infringement (see, e.g., MPEP § 2173, explaining the “primary purpose” of 35 USC § 112(b)). Accordingly, such assertions fail to address the merits of the rejection based upon MPEP § 2173.05(g), because the claim continues to simply “recite a description of a problem to be solved or a function or result achieved by the invention”, without providing a meaningful definition of what exact compounds are included or excluded by the phrase “an antagonist of Big Potassium (BK) channel activity”.
Third, it is the Examiner’s understanding that Applicant alleges that the meaning of the unclaimed term “ion channel antagonist” is known in the art (see, e.g., Reply filed 12/01/2025 at 7-8 at bridging ¶). This is moot because “ion channel antagonist” is not recited in the claim or at issue. Rather, the claim recites “an antagonist of Big Potassium (BK) channel activity….wherein the antagonist reduces said increased BK channel activity” and wherein the “increased BK channel activity” is specifically attributable to “one or more UBE3A mutations” that “result in loss or reduction of UBE3A function that causes increased BK channel activity” (see claim 14). This is not synonymous or equivalent to “ion channel antagonist”. Accordingly, arguments pertaining to unclaimed terms is not persuasive and fails to address the rejection based upon terms and phrases actually set forth in the claims.
Fourth, it is the Examiner’s understanding that Applicant alleges that
“a skilled artisan can therefore easily identify whether any compound (be it paxilline, IBTX, GAL021, or a new analog, etc.) falls within the scope of the present claims by determining whether it antagonizes BK channel activity and ameliorates seizures caused by that specific functional defect . . . using routine assays as disclosed in the specification”
(see, e.g., Reply filed 12/01/2025 at 8 at last three ¶¶).
Assertions that “an artisan can figure it out” do not reflect the test nor standard for satisfying the requirements of USC § 112(b). Rather, the relevant test is whether or not an artisan, in view of the instant application, could meaningfully identify the boundaries of the claim scope in order to avoid infringement (see, e.g., MPEP § 2173, explaining the “primary purpose” of 35 USC § 112(b)). Accordingly, arguments premised upon requiring an artisan to repeatedly infringe upon a claimed invention to determine the scope of the claim does not reflect the requirements and purpose of 35 USC § 112(b), and therefore are not persuasive.
Fifth, the lack of clear metes and bounds of the phrase “an antagonist of Big Potassium (BK) channel activity” is illustrated by Applicant’s own arguments attempting to differentiate the pending claim scope from the prior art of US20090247607 (see Reply filed 12/01/2025 at p. 15 at 1st full ¶). Specifically, the rejection identifies that dsRNA targeting E6AP (i.e., UBE3) is an “antagonist” of BK channel activity, and specifically “wherein the ‘activity’ is BK channel ubiquitination and proteasomal degradation mediated by UBE3A, and wherein targeting UBE3A with dsRNA would antagonize this ‘activity’” (see rejection over US’607, above). However, Applicant alleges that such “activity” (and therefore such antagonist) is excluded from the scope of the term “an antagonist of Big Potassium (BK) channel activity” because the “activity” is allegedly limited to “BK channel ion-conductance” (see Reply filed 12/01/2025 at p. 15 at 1st full ¶), and therefore excludes antagonists of BK channel ubiquitination and proteasomal degradation mediated by UBE3A. However, no such definition or guidance appears on record supporting this preferred definition, and any specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer). Accordingly, the Applicant’s own response illustrates the ambiguity of the Applicant’s functionally defined genus of compounds.
Accordingly, all arguments pertaining to the phrase “an antagonist of Big Potassium (BK) channel activity” have been fully considered, but such arguments have not identified how such language corresponds to a meaningful structure/function relationship permitting an artisan to identify and distinguish infringing from non-infringing embodiments in order to avoid infringement of the claimed invention. The courts have stated
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
A disclosure requiring an artisan to “figure out” what does or does not infringe a claim cannot be reasonably said to provide a description of a compound sufficient to permit an artisan to avoid infringement. Accordingly, the rejection is maintained (see MPEP § 2173.05(g)).
It is the Examiner’s understanding that Applicant is alleging that the patient populations defined by a condition “in a subject”, wherein the condition is “seizures caused by one or more [UBE3A] mutations in a subject”, wherein “the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity” (claims 14 and 22), or the patient populations defined as “a related autism spectrum disorder caused by loss or reduction of UBE3A” are not indefinite, and that such functional definitions satisfy the requirements of 35 USC § 112(b) (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶ to 9 at 1st partial ¶). The applicable arguments are addressed below.
First, it is the Examiner’s understanding that Applicant alleges that the claims now “define the specific disease mechanism” (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶). This is factually incorrect. Although Applicant has recited a functional definition delineating a hoped-for and desired genus, it is prima facie not a “specific disease mechanism” in the absence of clarification regarding what exact mutations of UBE3A do or do not satisfy the functional limitations, and thereby define a patient population. UBE3A is over 5000 nucleotides in length, and it is unknown what mutations in UBE3A do or do not cause both “loss or reduction of UBE3A” of an unspecified function, as well as “causes increased BK channel activity”, wherein the specific activity is unspecified. Such mutations may be SNPs, insertions, deletions, truncations, and may even be within promoter regions of the gene or in untranslated regions of the mRNA--but no guidance commensurate in scope with the claims is provided in the originally filed disclosure. Accordingly, the conclusory statement that a “specific disease mechanism” is recited is not supported by objective evidence addressing the merits of the rejection in view of MPEP § 2173.05(g).
Second, it is the Examiner’s understanding that Applicant alleges that the claims
…clearly define[] the pathological mechanism in measurable physiological terms….can be quantified by standard electrophysiological methods…. Routinely assessed using Wstern blot or sequencing assays”
(see, e.g., Reply filed 12/01/2025 at 7-8 at bridging ¶).
Assertions that “an artisan can figure it out” do not reflect the test nor standard for satisfying the requirements of USC § 112(b). Rather, the relevant test is whether or not an artisan, in view of the instant application, could meaningfully identify the boundaries of the claim scope in order to avoid infringement (see, e.g., MPEP § 2173, explaining the “primary purpose” of 35 USC § 112(b)). Evidence that Applicant possessed and defined methods already known in the prior art is not equivalent to evidence that Applicant provided a description of a patient population sufficient to permit an artisan to avoid infringement, since utilizing and confirming the claim scope would entail infringing the claimed invention. Accordingly, arguments premised upon requiring an artisan to repeatedly infringe upon a claimed invention to determine the scope of the claim does not reflect the requirements and purpose of 35 USC § 112(b), and therefore are not persuasive.
Third, it is the Examiner’s understanding that Applicant is alleging that “related autism spectrum disorder caused by loss or reduction of UBE3A” is definite (see, e.g., Reply filed 12/01/2025 at 8 at penultimate ¶). This phrase is undefined on record (and constitutes new matter), and therefore it is unclear how Applicant’s conclusory statement (see id) addresses the merits of the rejection. It remains unknown and uncertain what diseases, disorders, and patient populations are included or excluded by such functional descriptions, because the functional descriptions fail to meaningfully correspond to any clear definition or description of record. For example, if an Artisan treated any possible patient having Asperger’s Syndrome, PDD-NOS, CDD, Rett Syndrome, etc., would that artisan be infringing upon the instant claim or not? Accordingly, such arguments fail to address the merits of the rejection by meaningfully clarifying the scope of the claims.
Fourth, it is unclear if the language at claims 14 and 22 encompass all patients diagnosed with Angelman Syndrome, or if only a subpopulation is included, since the specification admits that UBE3A loss of function do not account for 100% of AS cases, and that “no concurrent mechanism has been fully established”, and that “neither the pathological mechanism underlying AS nor the biological substrate(s) of UBE3A have been characterized11. Accordingly, assertions that the claims now “define the specific disease mechanism” (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶) do not reflect the originally filed disclosure, which contradicts such assertions.
Accordingly, all arguments pertaining to the functionally defined patient population have been fully considered, but such arguments have not identified how such language corresponds to a meaningful structure/function relationship permitting an artisan to identify and distinguish infringing from non-infringing patient populations in order to avoid infringement of the claimed invention. A disclosure requiring an artisan to “figure out” what does or does not infringe a claim cannot be reasonably said to provide a description sufficient to permit an artisan to avoid infringement. Accordingly, the rejection is maintained (see MPEP § 2173.05(g)).
Although Applicant appears to allege that “an objective functional boundary” exists after amendment (see, e.g., Reply filed 12/01/2025 at 7 at 2nd full ¶), Applicant fails to explicitly identify what structures, concentrations, routes of administration, and patient populations are actually included or excluded from the amended claim scope. Furthermore, the alleged “objective functional boundary” (see id.) fails to correspond to any meaningful structure/function relationship of record that reasonably permits artisans to identify the metes and bounds of the claimed subject matter without potentially infringing.
Accordingly, all arguments pertaining to 35 USC 112(b) have been fully considered but not found persuasive. Failure to specifically address the merits and legal basis of each rejection combined with conclusory statements, and rationales that do not reflect US patent practice is insufficient to rebut the rejections under 35 USC 112(b) as set forth above. Accordingly, the amended claims remain rejected for the reasons set forth above in the new and revised rejections, which were necessitated by Applicant’s amendments.
35 USC 112(a), Written Description
It is the Examiner’s understanding that Applicant addresses the rejections under 35 USC 112(a) (written description) at pages 9-14 of the Reply (see, e.g., Reply filed 12/01/2025 at 9 at 2nd full ¶ to 14 at 1st full ¶). Arguments pertaining to withdrawn claims or withdrawn rationales not maintained above, are moot. Remaining applicable arguments have been fully considered, but not found persuasive for the reasons discussed below.
The discussion and responses set forth above in response to the arguments regarding 35 USC 112(b) under MPEP § 2173.05(g) are incorporated herein, because such rationales address ill-defined functional limitations, and structure/function relationships are relevant to the analysis under USC 112(a).
It is the Examiner’s understanding that Applicant repeatedly relies upon conclusory statements and terms (i.e., “diagnostic criteria”, “measurable mechanistic state”, “the skilled artisan can thus unambiguously identify patients who fall within the claimed method”, “the functional definition in amended claim 14 is both objective and diagnostic”, the claims “now define a functionally unified genus rather than a structurally arbitrary collection”, “The functional limitation provides an experimentally verifiable boundary”, “detailed mechanistic framework”, etc., etc.; see, e.g., Reply filed 12/01/2025 at 9 at 2nd full ¶ to 14 at 1st full ¶). Examiner notes that conclusory statements, ambiguous terms, and ambiguous phrases that do not clearly identify a supporting disclosure within the originally filed disclosure or prior art, by unambiguous citation, combined with an explanation of how such cited evidence supports that such term or phrase is adequately described sufficient to satisfy 35 USC 112(a), is understood to be arguments of counsel unsupported by objective evidence. All cited evidence corresponding to a particular functional term or phrase has been fully considered as set forth below.
It is the Examiner’s understanding that Applicant’s position is that possession of methods usable in the discovery of novel compounds, mutations, and patient populations as required to practice the claimed invention is equivalent and sufficient to establish possession of the full scope of the claims commensurate in scope with the requirements of 35 USC §112(a) (see, e.g., Reply filed 12/01/2025 at 9 at 2nd full ¶ to 14 at 1st full ¶). This line or reasoning does not reflect US Patent practice for 35 USC 112(a) because possessing a method evidences possession of the method; however, possession of a method does not equate to possession of all compounds discoverable or synthesizable by a method. For example, possession of FMOC peptide synthesis does not automatically equate to possession of all possible protein sequences synthesizable by FMOC peptide synthesis methods. Likewise, possession of an idea for a screening method of identifying UBE3A mutations that increase some unspecified BK channel activity does not automatically equate to possession of all possible mutations that actually yield that result, since it remains undiscovered what actual mutations (from among >thousands possible) actually do or do not achieve the desired and hoped for effect. Similarly, possession of an idea of what functional result a structure should perform does not automatically equate to possession of all possible chemical structures capable of performing the desired and hoped for functional result. Rather, the courts have explained that the description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Furthermore, the courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). Here, the functional language relied upon is equivalent to “merely drawing a fence around a perceived genus”, while “leaving it to others to explore the unknown contours of the claimed genus”, since the disclosure fails to actually identify what specific structures qualify as “antagonists” as claimed.
It is the Examiner’s understanding that the Applicant refers to paxilline, IBTX, and GAL-021 as representative species “an antagonist of Big Potassium (BK) channel activity” (see, e.g., Reply filed 12/01/2025 at 11 at 1st full ¶). The claimed invention is directed to an in vivo treatment methodology, and only paxilline was tested in vivo and shown to achieve the claimed outcome (i.e., treating seizures) within a limited dosage range, but the claims are not limited to paxilline or the limited dosage range (see, e.g., Spec. filed 6/16/2022 at 36 at lines 10-25, noting that the sole embodiment reduced to practice showed that the tested compound only worked as intended at concentrations at 0.35 mg/kg to under 3 mg/kg because 3 mg/kg “resulted in increased seizure susceptibility in WT mice”, and “10 mg/kg paxilline caused seizures in WT and KO mice”). Accordingly, zero species of the claimed invention utilizing IBTX or GAL-021 were reduced to practice, and therefore it is prima facie unknown what the therapeutic window of IBTX or GAL-021 might be, since the only data of record shows that paxilline causes seizures if utilized outside a narrow therapeutic window. Upon review of the Applicant’s response, it appears the Applicant fails to address this issue in any claim other than instant claim 20 (see, e.g., Reply filed 12/01/2025 at 12 at final ¶ to p. 13 at penultimate ¶). Accordingly, zero amendments addressing such issues appear in pending claims 14-16, 19, or 22-24. Accordingly, such issue persists for such claims and continues to necessitate a rejection under 35 USC 112(a).
It is the Examiner’s understanding that Applicant is alleging that the patient populations defined by a condition “in a subject”, wherein the condition is “seizures caused by one or more [UBE3A] mutations in a subject”, wherein “the one or more UBE3A mutations result in loss or reduction of UBE3A function that causes increased BK channel activity” (claims 14 and 22; see also Reply filed 12/01/2025 at 9-10 at bridging ¶, 10 at 1st full ¶ to 12 at 2nd full ¶). However, the only “mutation” tested was KO mice using paxilline (see, e.g., Spec. filed 6/16/2022 at 36 at lines 10-25). This is pertinent because the proffered data at Example 6 is limited to UBE3A KO mice (mice with maternal Ube3a deletion) (see, e.g., Spec. filed 6/16/2022 at 34-36 at § Example 6), which does not meaningfully place the Applicant in possession of any single “mutations” at any particular position or domain within UBE3A (i.e., the mRNA transcript for UBE3A is over 5000 nucleotides in length) that actually “result in loss or reduction of UBE3A function that causes increased BK channel activity”. For example, if the protein of UBE3A is mutated (i.e., deleted, altered by insertion, substituted) at position X, wherein X can be any position within the UBE3A protein, it is unclear if that mutation actually “results in loss or reduction of UBE3A function that causes increased BK channel activity”. Although such information is discoverable using screening methods and brute-force testing, the possession of an idea for screening is not equivalent to possession of a specific subset of UBE3A mutations actually required to identify the patient population encompassed by the instant claims. Rather, the courts have explained that the description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate."). Furthermore, the courts have stated that “merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus” (see, e.g., AbbVie v. Janssen, 111 USPQ2d 1780 (Fed. Cir. 2014) at 1789). Here, the functional language relied upon is equivalent to “merely drawing a fence around a perceived genus”, while “leaving it to others to explore the unknown contours of the claimed genus”, since the disclosure fails to actually identify what specific structures qualify as “antagonists” as claimed.
Claims 14, 16, 19, and 23 are not limited to paxilline, IBTX, or GAL021. Although, it is the Examiner’s understanding that the Applicant refers to paxilline, IBTX, and GAL-021 as representative species “an antagonist of Big Potassium (BK) channel activity” (see, e.g., Reply filed 12/01/2025 at 11 at 1st full ¶), this is unsupported by objective evidence because it is unclear how such structures reasonably represent, or otherwise inform artisans of completely different compounds, that would presumably function via different mechanistic pathways, including siRNA, aptamers, antisense molecules (LNAs, PNAs, MOEs, etc.), unspecified small molecules, and other compounds that constitute “an antagonist of BK channel activity” (proteins, antibodies, etc.?). Notably, Applicant fails to identify any disclosure regarding what does or does not constitute a “therapeutically effective amount” of any compound in any subject having any mutation other than a Ube3am-/p+ KO. Furthermore, Applicant fails to identify what does or does not constitute a “therapeutically effective amount” of siRNA, IBTX, GAL021, aptamers, antisense molecules (LNAs, PNAs, MOEs, etc.), unspecified small molecules, etc. in any in vivo system sufficient to reduce seizures without causing more seizures. Such disclosure is relevant since the record shows that even in the only in vivo model tested, that the tested compound actually induced seizures when utilized outside of a narrow therapeutic window (see, e.g., Spec. filed 6/16/2022 at Example 6 and p. 36 at lines 10-25). Accordingly, zero evidence reasonably informing an artisan of whether or not, in humans diagnosed with Angelman Syndrome, administration of 1, 2, 3, 4, …. mg of IBTX, GAL021, etc. would treat seizures or cause seizures. In the absence of such basic clinical information, it cannot reasonably be concluded that Applicant has provided evidence of “possessing” such claim scope commensurate in scope with 35 USC 112(a).
The courts have held that a claim to a therapeutic method requiring administration of an “effective” amount of a compound (i.e., a specific dosage range) set forth in the disclosure for the treatment of a broad array of disorders failed to satisfy the Written Description Requirement because the disclosure addressed only “basic research and broad []dosage ranges”, but did not establish possession of a “therapeutically effective [] dose at the time of filing” (see, e.g., Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *8 (Fed. Cir. 2021). The court clarified that although
An inventor need not "prove that a claimed pharmaceutical compound actually achieves a certain result. But when the inventor expressly claims that result, our case law provides that [such] result must be supported by adequate disclosure in the specification.”
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1343 (Fed. Cir. 2021).
The court further explained that
That Biogen later established the therapeutic efficacy of [a known compound at a specific dosage] is of no import to the written-description analysis. What matters for purposes of the inquiry [*1344] in this case is whether, at the time of filing the disclosure—well before the Phase III study even commenced—a skilled artisan could deduce simply from reading the specification that [a known compound at a specific dosage] would be a therapeutically effective treatment for MS. As to this point, the specification's focus on drug discovery and basic research further buttresses the district court's conclusion that the specification lacks an adequate written description to support the [] claims. . . . the law is clear that a patent cannot be awarded for mere theoretical research without more, see Ariad, 598 F.3d at 1353 . The written-description requirement limits patent protection only to individuals who perform the difficult work of producing a complete and final invention featuring all its claimed limitations and publicly disclose the fruits of that effort.
See Biogen Int'l GmbH v. Mylan Pharm. Inc., 18 F.4th 1333, 1344, 2021 U.S.P.Q.2d 1170, 2021 BL 455178, at *9 (Fed. Cir. 2021); emphasis added
Here, like in Biogen, the Specification is directed to basic research without clear clinical data sharing a nexus with the claims because, at best, one narrow species of the claimed invention applicable only to a single compound used within a very narrow therapeutic window in a single maternal gene KO was actually reduced to practice or discussed with specificity. Furthermore, unlike Biogen, here the claims further attempt to draw a fence around the treatment of all possible species of any “seizures” in any disease, syndrome, or disorder “caused by one or more [UBE3A] mutations in a subject”, wherein the “mutations” are not limited to a maternal deletion and zero specific single residue mutation are discussed on record, and wherein “the one or more UBE3A mutations” are limited to a completely unknown genus of mutations that “result in loss or reduction of UBE3A function that causes increased BK channel activity” (claims 14 and 22), using any possible “effective” concentrations, via all possible routes of administration, in all possible patient populations encompassed by the functional language. Therefore, the instant claims are substantially broader in scope than the claims of Biogen, but the disclosure of the instant Specification appears to provide substantially less guidance than that of the specification at issue in Biogen. Therefore, like Biogen, the instant claims lack written description support because an artisan “simply from reading the specification” could not deduce which compound at what concentration would be “effective” for the treatment of any particular disease, condition, or syndrome characterized by seizures and UBE3A mutations, as presently claimed.
It is the Examiner’s understanding that Applicant’s position is that the originally filed disclosure may render obvious the pending claim scope (see, e.g., Reply filed 12/01/2025 at 9 at 2nd full ¶ to 14 at 1st full ¶). However, obviousness is not the test for written description support. Although the originally-filed disclosure may render the instant claims obvious, “a description which renders obvious a claimed invention is not sufficient to satisfy the written description requirement of that invention” (see, Regents of the University of California v. Eli Lilly, 119 F.3d 1559, 1567 (Fed. Cir. 1997)) because “[o]ne shows that one is ‘in possession’ of the invention by describing the invention, with all its claimed limitations, not that which makes it obvious” (Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1571-72 (Fed. Cir. 1997) at 1572).
Accordingly, all arguments pertaining to 35 USC 112(a) have been fully considered but not found persuasive as set forth above. Accordingly, the amended claims remain rejected for the reasons set forth above in the new and revised rejections, which were necessitated by Applicant’s amendments.
35 USC 103, US20090247607
It is the Examiner’s understanding that Applicant addresses the rejections under 35 USC 103 with respect to US’607 at pages 14-17 of the Reply (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶). Arguments pertaining to withdrawn claims or withdrawn rationales not maintained above, are moot. Remaining applicable arguments have been fully considered, but not found persuasive for the reasons discussed below.
It is the Examiner’s understanding that Applicant refers to the application rather than the claimed invention, or otherwise refers to unclaimed limitations (see, e.g., Reply filed 12/01/2025 at 14 at final ¶ referring to “therapeutic restoration of BK channel homeostasis”, 14 at final ¶ referring to what “the instant application establishes”, 14 at final ¶ referring to “pathological BK channel overactivity” and “normal excitability”, 15 at 1st full ¶ referring to “mechanistic[]” limitations, 15 at 1st full ¶ referring to inhibition of “BK channel ion-conductance”, 16 at 1st partial ¶ referring to “downstream BK channel overactivity”, 16 at 2nd bullet referring to antagonists that “reduce BK channel conductance”, etc.). In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). Accordingly, such arguments are not persuasive because they fail to identify how the claimed invention is distinguishable from the prior art invention.
It is the Examiner’s understanding that Applicant attempts to differentiate the prior art relative to the instant invention by invoking a specialized definition of “activity” within the phrase “an antagonist of Big Potassium (BK) channel activity” and “BK channel activity”, by alleging that “activity” is limited to “BK channel ion-conductance” but excludes “UE3A’s ubiquitin-ligase activity” (see, e.g., Reply filed 12/01/2025 at 15 at 1st full ¶). Applicant fails to identify any supporting disclosure for this specialized definition. Applicant is advised that any specialized definition must be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer). In the absence of any specialized definition, the “activity” of the BK channel is given the broadest reasonable interpretation, which includes broadly includes all activities attributable to a “BK channel”, including ion-channel conductance, BK channel ubiquitination and proteasomal degradation mediated by UBE3A, BK Channel expression (i.e., mRNA transcript production), BK Channel protein expression (i.e., mRNA translation rate), BK Channel binding, BK Channel membrane trafficking, etc., etc. Accordingly, arguments premised upon a specialized definition unsupported by the originally filed disclosure or any cited evidence, is not persuasive.
Allegations suggesting “skepticism of experts”: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the Examiner’s position would be met with skepticism of experts Reply (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 15 at 1st ¶ to 17 at 1st partial ¶). If Applicant means to suggest the existence of skepticism of experts, such evidence should be filed per MPEP § 716.05 as evidence is required to establish skepticism of experts. In the absence of such evidence, such statements are understood to be unsupported conjecture of counsel. The prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)), and no objective evidence rebutting this presumption has been placed on record to date.
Allegations suggesting “inoperability” or lack of enabling disclosure regarding a prior art reference: It is the Examiner’s understanding that Applicant’s statements amount to a suggestion that the prior art is not fully enabled or operable (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 15 at 1st ¶ to 17 at 1st partial ¶). If Applicant is attempting to allege that the prior art is not enabling or inoperable Applicant is directed to MPEP § 2121(I), which notes that the prior art is presumed fully enabled for all that it discloses, and the burden is on the Applicant to rebut the presumption of operability (see, e.g., MPEP § 2121(I); MPEP § 716.07). No evidence of inoperability commensurate in scope with the requirements of MPEP § 716.07 have been placed on record at this time; critically, arguments of counsel cannot take the place of evidence in the record (see, e.g., In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965), and evidence is required to rebut the presumption of operability. The Examiner’s position is that the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), including “all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments” (see, e.g., MPEP § 2123(I)). Accordingly, the Applicant has not satisfied their burden to rebut the presumption of operability of the prior art at this time (see, e.g., MPEP § 2121(I); MPEP § 716.07).
Applicant has a different rationale for arriving at the instant invention: It is the Examiner’s understanding that Applicant identifies that their rationale for arriving at the claimed invention differs from the rationale relied upon by the Examiner to establish obviousness (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 15 at 1st ¶ to 17 at 1st partial ¶, alleging that the claimed invention is mechanistically distinct and based upon ion-channel conductance). Examiner notes that this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (see, e.g., MPEP § 2143(I)(A), (G)), and merely based upon the express disclosure teachings that dsRNA to patients with Angelman Syndrome at dosages “less than 5 mg/kg body weight” via intraperitoneal injection (see, e.g., US’607 at ¶¶[0068], [0099], [0104], [0131]12), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. Accordingly, it is neither disputed nor dispositive of obviousness that the Examiner did not support a rationale that was not actually relied upon in the rejection to establish prima facie obviousness.
Allegations suggesting the references “teach away”: It is the Examiner’s understanding that Applicant is suggesting that the references “teach away” from the claimed invention in view of the statements alleging that Benson allegedly states that such treatment would induce unwanted conditions (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 15 at 1st ¶ to 17 at 1st partial ¶). Examiner notes that this argument is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Applicant’s relies upon a quote, taken out of context, and is again directed to the entirety of the disclosure at US’607 at paragraph [0131]13. Accordingly, Applicant has not identified any disclosure that “criticizes, discredits, or otherwise discourages the solution claimed”. Accordingly, no “teaching away” has been identified on record.
Allegations suggesting “lack of predictability” or “lack of reasonable expectation of success”: It is the Examiner’s understanding that Applicant is alleging a lack of predictability or otherwise a lack of reasonable expectation of success (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 15 at 1st ¶ to 17 at 1st partial ¶). This is not persuasive because the Applicant’s assertions do not reflect the proper legal standards for evaluating predictability. MPEP § 2143.02(II) explains that “[o]bviousness does not require absolute predictability”, but instead clarifies that only “at least some degree of predictability is required” (see, e.g., MPEP § 2143.02(II)). Here, the rejection explicitly addresses predictability and reasonable expectation of success, but Applicant fails to address the explicitly identified predicted and expected results set forth in the rejection. Here, the Examiner’s basis for “predictability” is merely based upon the presumption that the prior art is fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). As explained at MPEP § 2143.02, predictability and reasonable expectation of success are satisfied when “all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art”. Here zero evidence of unexpected results commensurate in scope with the requirements of MPEP 716.02 have been set forth on record, all elements of the claimed invention were known in the prior art, one of ordinary skill was fully enabled to combined each component using routine methods in the biochemical arts per the guidance of the primary reference, and the elements would have merely performed their art-recognized, respective functions (see Rejection, above). Applicant’s position is understood to read upon a quote, taken out of context, and therefore Applicant is again directed to the entirety of the disclosure at US’607 at paragraph [0131]14, which identifies that “dsRNA targeting [UBE3A] may be employed to treat neurological and behavioral disorders . . . . Angelman syndrome”. Accordingly, absent objective evidence to the contrary, the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses and reasonably suggests. (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is the Examiner’s position that such dsRNA antagonists are fully encompassed by the pending claim scope. Accordingly, such arguments are not persuasive.
Allegations suggesting improper or impermissible hindsight: It is the Examiner’s understanding that Applicant is suggesting that the Examiner’s position fails to establish a prima facie case of obviousness because the prior art does not lead an artisan to the instant invention (see, e.g., Reply filed 12/01/2025 at 14 at 2nd full ¶ to 17 at 1st partial ¶; see esp. id. at 16 at final bullet). If Applicant means to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not taught, disclosed, or suggested by the prior art relied upon by the Examiner.
Documents or Evidence not of record: It is the Examiner’s understanding Applicant refers to documents or evidence not of record (see, e.g., Reply filed 12/01/2025 at 16 at final bullet, referring to “Published electrophysiology”, and the state of the art “At the time of filing”). Such references are understood to be arguments of counsel in the absence of objective supporting evidence. Applicant is advised that any documents or evidenced will be fully considered only after it is properly placed on record and properly cited in a manner permitting the Examiner to evaluate the referenced information.
Accordingly, all arguments pertaining to the rejection under 35 USC 103 in view of US’607 have been fully considered but not found persuasive as set forth above. In brief, the arguments failed to identify how the prior art differs from the invention as actually claimed. Accordingly, the amended claims remain rejected for the reasons set forth above in the new and revised rejections, which were necessitated by Applicant’s amendments.
35 USC 103, WO2017/075222, Pelc, and Sheehan.
It is the Examiner’s understanding that Applicant addresses the rejections under 35 USC 103 with respect to WO’222, Pelc, and Sheehan at pages 17-21 of the Reply (see, e.g., Reply filed 12/01/2025 at 17 at 1st full ¶ to 21 at final ¶). Arguments pertaining to withdrawn claims or withdrawn rationales not maintained above, are moot. Remaining applicable arguments have been fully considered, but not found persuasive for the reasons discussed below.
Piecemeal Analysis of References: It is the Examiner’s understanding that Applicant repeatedly addresses and explains that individual references, when considered individually, do not anticipate or otherwise render obvious the claimed invention (see, e.g., Reply filed 12/01/2025 at 17-18 at bridging ¶ addressing Maher alone, 18-19 at bridging ¶ addressing Sheehan alone, 19-20 at bridging ¶ addressing references individually). In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The rejection is based upon a combination of three references considered together, and no rejection alleging obviousness or anticipation over the individual references appears on record.
Conclusory Statements: Examiner notes that conclusory assertions made in the absence of any objective evidence, explanation, analysis or case law, are understood to be arguments of counsel unsupported by objective evidence, and therefore not persuasive (see, e.g., Reply filed 12/01/2025 at 19 at 1st full ¶).
It is the Examiner’s understanding that Applicant addresses the three references individually rather than in combination (see, e.g., Reply filed 12/01/2025 at 19-20 at bridging ¶), and provides a conclusory statements amounting to a dismissal of the combined teachings of the references and the merits of the rejection, above. As explained in the rejection, the primary reference establishes that Paxilline would have already been administered to the same or overlapping patient population via the same administration route and at the same or overlapping concentration, in order to predictably treat any neurodevelopmental disorder known in the prior art (see discussion regarding WO’222, above), which, as established by Pelc, would have already included Angelman syndrome. Accordingly, Angelman syndrome would be reasonably inferred to be within the scope of WO’222. Furthermore, Angelman syndrome was known in the art to be associated with seizures, and Sheehan identifies that Paxilline would also desirably and beneficially be expected and predicted to treat seizures. Accordingly, the rejection is based upon the simple conclusion that, upon following the guidance of the primary reference to treat the neurodevelopmental disorder of Angelman syndrome by administering Paxilline in the amounts taught by WO’222, an artisan would have readily predicted and expected that such treatment would desirably treat Angelman syndrome and artisans would have also have a reasonable expectation that such treatment would also desirably and expectedly treat seizures associated with Angelman syndrome in view of Sheehan (see, e.g., MPEP § 2143(I)(A), (F), (G)), because each element merely performs its art-recognized function. Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to treat a known patient population having a known neurodevelopmental disorder with a known compound at a known dosage and known route of administration, exactly as taught and suggested by the primary reference. Applicant fails to identify a single claimed limitation that was not addressed by the rejection, and Applicant fails to distinguish how the claimed invention excludes the teachings of the prior art. Accordingly, such arguments are not persuasive.
Documents or Evidence not of record: It is the Examiner’s understanding Applicant refers to documents or evidence not of record (see, e.g., Reply filed 12/01/2025 at 20 at 1st ¶), and upon this uncited information alleges what the “art viewed” at “the relevant date of filing” (see, e.g., Reply filed 12/01/2025 at 20 at 1st ¶). Such references are understood to be arguments of counsel in the absence of objective supporting evidence. Applicant is advised that any documents or evidence will be fully considered only after it is properly placed on record and properly cited in a manner permitting the Examiner to actually evaluate the referenced information. In the absence of such objective evidence, such comments amount to arguments of counsel unsupported by objective evidence. Furthermore, such comments fail to materially identify how the claimed invention is non-obvious in view of the art of record.
Allegations suggesting the references “teach away”: It is the Examiner’s understanding that Applicant is suggesting that uncited information “teach away” from the claimed invention (see, e.g., Reply filed 12/01/2025 at 20 at 1st ¶). Examiner notes that this argument is not persuasive because none of prior art references at issue “teach away” from the claimed invention since they do not actually “criticize, discredit, or otherwise discourage the solution claimed” (see, e.g., MPEP § 2141.02(VI)). Accordingly, no “teaching away” has been identified on record.
Applicant has a different rationale for arriving at the instant invention: It is the Examiner’s understanding that Applicant identifies that their rationale for arriving at the claimed invention differs from the rationale relied upon by the Examiner to establish obviousness (see, e.g., Reply filed 12/01/2025 at 20 at 1st ¶, referring to Applicant’s discovery and alleged “central mechanism”). Examiner notes that this is not persuasive because an examiner may support a determination of obviousness by relying upon a rationale that differs from the Applicant’s rationale (see, e.g., MPEP § 2144(IV)). Here, the Examiner’s rationales are explicitly identified in the rejection (i.e., MPEP § 2143(I)(A), (F), (G)), but Applicant fails to address or specifically dispute these rationales supporting a determination of obviousness. Accordingly, it is neither disputed nor dispositive of obviousness that the Examiner did not support a rationale that was not actually relied upon to establish prima facie obviousness.
It is the Examiner’s understanding that Applicant is alleging what the “instant application provides” (see, e.g., Reply filed 12/01/2025 at 20 at penultimate ¶). The rejection is over the claimed invention, not the application. Accordingly, such arguments are moot because they do not meaningfully identify how the claimed invention, as actually claimed, is non-obvious over the teachings of the prior art.
It is the Examiner’s understanding that Applicant is alleging what the “inventors have discovered” (see, e.g., Reply filed 12/01/2025 at 20-21 at bridging ¶). The rejection is over the claimed invention, not an unclaimed discovery. Accordingly, such arguments are moot because they do not meaningfully identify how the claimed invention, as actually claimed, is non-obvious over the teachings of the prior art.
It is the Examiner’s understanding that Applicant is alleging
…Applicant respectfully highlights that the International Preliminary Report on Patentability (IPRP) for PCT/SG2020/050762 has indicated that the there is no clear teaching or suggestion in the prior art documents that would motivate a skilled person to select a BK channel antagonist for treating seizure caused by UBE3A mutations in a subject, and thus the BK channel antagonist in the treatment of seizure caused by UBE3A mutations in a subject is novel and inventive.
(see, e.g., Reply filed 12/01/2025 at 21 at 1st full ¶).
Although moot in view of the rejections above and the fact that US patent law is controlling, and that the instant search is more extensive because it is in addition to the one provided in the WO of the ISA, Examiner further notes that this conclusion is misleading because PCT/SG2020/050762 actually stated that therapeutic methods are excluded subject matter under the PCT Rule 39.1(iv), and only proffered opinions based upon presumed redrafting of such claims to a presently unclaimed format (see WO of the ISA at Box V(2)). Notably, the WO of the ISA does explain that “[a] mere discovery of mechanism is insufficient in conferring novelty to a medical use claim” (see WO of the ISA at Box V(2)(1. Novelty)). Similarly, as noted above, the treatment of Angelman Syndrome by administering paxilline to the same or overlapping patient population via the same administration route and at the same or overlapping concentration, in order to predictably treat any neurodevelopmental disorder was already known in the prior art. Simply following this guidance by administering paxilline to patients to treat such disorders therefore satisfies all active “hand-of-man” steps presently claimed. Furthermore, the additional benefits of treating seizures is merely an additional advantage of following the prior art guidance. The fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). Accordingly, such arguments are not persuasive because they fail to distinguish the presently claimed invention relative to the prior art of record, by addressing the merits of the rejection.
Allegations suggesting improper or impermissible hindsight: It is the Examiner’s understanding that Applicant is suggesting that the Examiner’s position fails to establish a prima facie case of obviousness because the prior art does not lead an artisan to the instant invention (see, e.g., Reply filed 12/01/2025 at 21 at final ¶). If Applicant means to suggest that the Examiner arrived at the instantly claimed invention via the use of improper hindsight, this is not persuasive because any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, Applicant fails to identify a single aspect of the claimed invention that was not taught, disclosed, or suggested by the prior art relied upon by the Examiner.
Accordingly, all arguments pertaining to the rejection under 35 USC 103 in view of WO’222, Pelc, and Sheehan have been fully considered but not found persuasive as set forth above. In brief, the arguments failed to identify how the prior art differs from the invention as actually claimed. Furthermore, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Accordingly, the amended claims remain rejected for the reasons set forth above in the new and revised rejections, which were necessitated by Applicant’s amendments.
Examiner Suggestion
Examiner suggests narrowing the claim scope as shown below:
A method of treating seizures in a subject having Angelman Syndrome, wherein treatment comprises administering paxilline to the subject intraperitoneally at 0.3 mg/kg to 3 mg/kg body weight of the subject.
Such claim scope would overcome the 112(a) and 112(b) rejections of record, and would overcome the 35 USC 103 rejection over US’607. Accordingly, such amendments would substantially simplify prosecution.
However, Applicant is advised that even the simplified and narrower scope identified above would continue to be rejected as obvious under 35 USC 103 in view of WO’222, Pelc, and Sheehan. However, this remaining rejection could potentially be addressed by providing evidence of unexpected results and criticality of range commensurate in scope with the requirements of MPEP § 716.02, sufficient to rebut prima facie obviousness.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Galván-Manso15 discusses Angelman syndrome (see, e.g., id. at title, abs, passim), associated with seizures, which were commonly treated by administering antiepileptic drug(s) to a patient in need (see, e.g., id. at 24).
N'Gouemo16 identifies that circa 2011, Paxilline was an art-recognized BK channel antagonist and recognized as capable of treating seizures and utility as an antiepileptic drug (see, e.g., N’Gouemo at 6-7 at bridging ¶, 11 at §2.5.3).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new or revised ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Pelc et al., Epilepsy in Angelman syndrome. Seizure. 2008 Apr;17(3):211-7. doi: 10.1016/j.seizure.2007.08.004. Epub 2007 Sep 29. PMID: 17904873
2 Sheehan et al., Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia. 2009 Apr;50(4):711-20. doi: 10.1111/j.1528-1167.2008.01888.x. Epub 2008 Nov 19. PMID: 19054419; cited in Requirement mailed 4/11/2025.
3 See, e.g., Spec. filed 5/16/2022 at 1 at lines 9-30, noting that UBE3A loss of function do not account for 100% of AS cases, and that “no concurrent mechanism has been fully established”, and that “neither the pathological mechanism underlying AS nor the biological substrate(s) of UBE3A have been characterized”.
4 See, e.g., Spec. filed 5/16/2022 at 1 at lines 9-30, noting that UBE3A loss of function do not account for 100% of AS cases, and that “no concurrent mechanism has been fully established”, and that “neither the pathological mechanism underlying AS nor the biological substrate(s) of UBE3A have been characterized”.
5 See, e.g., Spec. filed 6/16/2022 at 34-36 at § Example 6.
6 See, e.g., Spec. filed 5/16/2022 at 1 at lines 9-30, noting that UBE3A loss of function do not account for 100% of AS cases, and that “no concurrent mechanism has been fully established”, and that “neither the pathological mechanism underlying AS nor the biological substrate(s) of UBE3A have been characterized”.
7 Noting that [0131] literally states “the dsRNA targeting E6AP may be employed to treat neurological and behavioral disorders. EP6A has been implicated in neurological and behavioral disorders through the identification of E6AP mutations in patients having Angelman syndrome….”
8 Pelc et al., Epilepsy in Angelman syndrome. Seizure. 2008 Apr;17(3):211-7. doi: 10.1016/j.seizure.2007.08.004. Epub 2007 Sep 29. PMID: 17904873; cited in previous action.
9 Sheehan et al., Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia. 2009 Apr;50(4):711-20. doi: 10.1111/j.1528-1167.2008.01888.x. Epub 2008 Nov 19. PMID: 19054419; cited in Requirement mailed 4/11/2025; cited in previous action.
10 see MPEP § 2144.05(I), noting in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists, and that similarly, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close.
11 See, e.g., Spec. filed 5/16/2022 at 1 at lines 9-30, noting that UBE3A loss of function do not account for 100% of AS cases, and that “no concurrent mechanism has been fully established”, and that “neither the pathological mechanism underlying AS nor the biological substrate(s) of UBE3A have been characterized”.
12 Noting that [0131] literally states “the dsRNA targeting E6AP may be employed to treat neurological and behavioral disorders. EP6A has been implicated in neurological and behavioral disorders through the identification of E6AP mutations in patients having Angelman syndrome….”
13 Noting that [0131] literally states “the dsRNA targeting E6AP may be employed to treat neurological and behavioral disorders. EP6A has been implicated in neurological and behavioral disorders through the identification of E6AP mutations in patients having Angelman syndrome….”
14 Noting that [0131] literally states “the dsRNA targeting E6AP may be employed to treat neurological and behavioral disorders. EP6A has been implicated in neurological and behavioral disorders through the identification of E6AP mutations in patients having Angelman syndrome….”
15 Galván-Manso et al., Analysis of the characteristics of epilepsy in 37 patients with the molecular diagnosis of Angelman syndrome. Epileptic Disord. 2005 Mar;7(1):19-25. PMID: 15741136; cited in previous action.
16 N'Gouemo, Targeting BK (big potassium) channels in epilepsy. Expert Opin Ther Targets. 2011 Nov;15(11):1283-95. doi: 10.1517/14728222.2011.620607. Epub 2011 Sep 19. PMID: 21923633; PMCID: PMC3219529; cited in previous action.