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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/3/2025 has been entered.
Claims 1, 5, 9-19, 21, 25, 29-41 are pending in the application.
All previous rejection not reiterated in this office action are withdrawn.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 12, 14-17, 32, 36-39 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.
Regarding claim 12 and 32, the claims are indefinite because it is unclear when the genetic test takes place, before the administration of the ASO or following the administration of ASO?
Regarding claim 14-17 and 36-39, it is unclear what the dosages are for the loading dose and the maintenance doses. Does it mean a fixed dose of 100 mg in claim 1 and claim 21 are doses for both loading dose and maintenance dose, or other dosages are also encompassed by the claims.
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 1, 9-19, 21, 29-41 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 a method of treating amyotrophic lateral sclerosis (ALS) associated with a mutation in the superoxide dismutase (SOD1) gene in a human subject in need thereof comprising administering to the human subject by intrathecal administering a pharmaceutical composition in an amount sufficient to deliver a fixed dose of 100 mg of an antisense oligonucleotide comprising SEQ ID NO:1 or the structure recited in claim 21, does not reasonably provide enablement for preventing ALS using said antisense composition. 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/use the invention commensurate in scope with these claims.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue." These factors include, but are not limited to: (a) the nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
The nature of the invention
Claims 1 and 21 are drawn to a method of treating or preventing ALS associated with a mutation in the SOD1 gene by administering to the human subject a fixed dose of 100 mg ASO comprising SEQ ID NO: 1 or having the structure recited in claim 21.
The breadth of the claim
The claim scope of claims 1 and 21 and dependent claims thereof encompasses both treating and preventing ALS using the same ASO composition.
The teaching from the specification and the presence of working examples
The specification describes a trial design of compound A, the ASO comprising SEQ ID NO: 1, which is a randomized, placebo controlled, single ascending dose, and multiple ascending dose study in SOD1 ALS patients. The specification describes pharmacokinetics and pharmacodynamics of compound A in both SAD and MAD, and its effect for reducing CSF pNFH levels and a slowing of clinical decline compared to placebo. The specification does not teach whether said compound A may prevent ALS. As such, whether it may preventing ALS having SOD1 mutation is unpredictable.
The state of prior art and level of predictability in the art
The prior art teaches ALS is a neurodegenerative disease characterized by selective degeneration of motor neurons, leading to progressive muscle weakness and ultimately respiratory failure, and most ALS patients die within 2 to 5 years after the onset of the symptoms (Ou et al. Translational Neurodegeneration 2025, 14: 4, pages 1-13, p.4, 1st col., 2nd paragraph). Tofersen, the compound claimed in claim 1 and 21, which was approved in 2023, is for treating SOD1 pre-mRNA that suppresses mRNA expression. Ou teaches intrathecal injection to human ALS patients showed a slower decline in respiratory function and muscle strength in patients and thus received FDA approval (page 5, 2nd col., 1st paragraph). However, there is no teaching from prior art that Tofersen can preventing ALS, nor does any data demonstrates that ALS with SOD1 mutation may be prevented by Tofersen even 7 years after the effective filing date of the present application. As such, whether this drug may be used to prevent ALS in a human subject is unpredictable.
The amount of experimentation required
Based on the teaching from prior art and present application, there is no teaching whether ASO comprising SEQ ID NO: 1 may be used to prevent ALS with SOD1 mutation. The scope of the claims 1, 21 and dependent claims thereof clearly exceeds the teaching from the specification. Therefore, a skilled artisan would have to engage in undue experimentation to practice the claimed method to its full scope. The claimed invention thus is enabled to the scope as indicated above.
Allowable Subject Matter
Claims 5 and 25 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CELINE X QIAN whose telephone number is (571)272-0777. The examiner can normally be reached M-F (8-4:00).
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/CELINE X QIAN/Primary Examiner, Art Unit 1637