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 .
DETAILED ACTION
Applicant’s amendments and remarks filed on April 16, 2026 are acknowledged. Claims 3-4, 7, 13-14, 17, 21, 26, 31-55, and 58 have been canceled. Claims 1, 20, and 28 were amended. Claims 1, 2, 5, 6, 8-12, 15, 16, 18-20, 22-25, 27-30, 56, 57, 59, and 60 are pending.
Election/Restrictions
Claims 1, 2, 5, 6, 8-12, 15, 16, 18-20, 22-25, 27-30, 59, and 60 are allowable. Claims 56 and 57, previously withdrawn from consideration as a result of a restriction requirement, require all the limitations of an allowable claim. Pursuant to the procedures set forth in MPEP § 821.04(a), the restriction requirement between inventions I and II, as set forth in the Office action mailed on February 27, 2025, is hereby withdrawn and claims 56 and 57 are hereby rejoined and fully examined for patentability under 37 CFR 1.104. In view of the withdrawal of the restriction requirement, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claims 1, 2, 5, 6, 8-12, 15, 16, 18-20, 22-25, 27-30, 56, 57, 59, and 60 are examined on the merits herein.
Priority
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Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Withdrawn Objections
In view of Applicant’s amendments and response, the objection to claims 1 and 28 is withdrawn.
Withdrawn Rejections
In view of Applicant’s amendments and response, the 35 U.S.C 103 rejections are withdrawn.
Specification
The disclosure is objected to because of the following informality:
Page 125, line 20 reads in part “wherein the sequeces of the PCR primers” and should read “wherein the sequences of the PCR primers” (emphasis added).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 56 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1 to a subject suffering from myasthenia gravis, does not reasonably provide enablement for preventing myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1 to a subject suffering from myasthenia gravis. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to 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 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. All of the Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Breadth of claims and nature of the invention:
Claim 56 is drawn to a method for treating and/or preventing myasthenia gravis, wherein the method comprises administering an effective amount of the siRNA conjugate according to claim 1 to a subject suffering from myasthenia gravis. The broadest reasonable interpretation of claim 56 is that the method encompasses not only treating myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1, but also preventing myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1.
Amount of direction provided by the inventor and existence of working
examples:
The instant specification envisions the following:
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[page 6, second full paragraph].
Working example 1 discloses determining the IC50 value of C5 mRNA in HepG2 cells by siRNA conjugate. The results are summarized in Table 6 (reproduced below) and demonstrate that the siRNA conjugate of the disclosure has higher inhibitory activity in HepG2 hepatoma cells in vitro. According to Table 3 on page 118 of the specification, Conjugate 1 refers to SEQ ID NOS: 361 (sense) and 362 (antisense), Conjugate 2 refers to SEQ ID NOS: 363 (sense) and 364 (antisense), Conjugate 3 refers to SEQ ID NOS: 365 (sense) and 366 (antisense), Conjugate 4 refers to SEQ ID NOS: 367 (sense) and 368 (antisense), Conjugate 5 refers to SEQ ID NOS: 369 (sense) and 370 (antisense), Conjugate 6 refers to SEQ ID NOS: 371 (sense) and 372 (antisense), Conjugate 7 refers to SEQ ID NOS: 377 (sense) and 378 (antisense), and Conjugate 8 refers to SEQ ID NOS: 379 (sense) and 380 (antisense).
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Working example 2 discloses distribution of siRNA conjugates in various organs of C57 mice. Ten C57BL/6J female mice were subcutaneously injected with 1 x PBS and Cy5-siRNA 1, the Cy5-conjugate 1, the Cy5-siRNA 2, or the Cy5-conjugate 2. Only mice administered with the Cy5-labeled conjugates had significantly enhanced fluorescence signals in the liver areas thereof and mice administered with the Cy5-labeled siRNAs or 1 x PBS did not have any fluorescence signal in the liver areas thereof. Further, it was demonstrated that only the Cy5-conjugate 1 and the Cy5-conjugate 2 can be aggregated in a large amount in the liver and a small amount in the kidney, but not aggregated in other organs thus indicating that the conjugate can effectively deliver siRNA specifically to the liver. According to Table 4b on page 123 of the specification, the siRNA sequences in Cy5-labeled siRNA conjugates and Cy5-labeled siRNAs are as follows:
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However, the specification does not provide any working examples of preventing myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1.
State of the prior art, level of predictability in the art, and level of one of
ordinary skill:
Although post-filing, Grover et al. (Semin Neurol 2022) discloses that myopathies are disorders affecting the muscles with varied etiologies and presentations. Myasthenia gravis is a post synaptic antibody mediated disorder affecting neuromuscular transmission. Grover et al. also discloses that no preventive strategies exist for myopathies; however, depending on etiology, the severity and course can be modified by a targeted treatment approach [page 594, left column]. Furthermore, Grover et al. discloses that while there are no known ways to prevent the development of neuromuscular disorders such as myopathy and MG, anticipating and managing common complications of both the disease course and the treatments used are important to prevent severe morbidity and early mortality [page 604, left column, last paragraph].
A review of the prior art shows that the state of the art of preventing myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1 is immature and nascent.
Quantity of experimentation:
In view of the breadth of the claims which embrace treating and preventing myasthenia gravis, the state and level of predictability in the art, the lack of working examples to show preventing myasthenia gravis comprising administering an effective amount of the siRNA conjugate according to claim 1, and the failure to provide adequate guidance to overcome the state and level of predictability of the art, one of skill would have to perform undue experimentation in order to practice the invention commensurate in scope with the claims.
Allowable Subject Matter
Claims 1, 2, 5, 6, 8-12, 15, 16, 18-20, 22-25, 27-30, 57, 59, and 60 are allowed.
Conclusion
Applicant's amendment necessitated the new 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 CHRISTINA TRAN whose telephone number is (571)270-0550. The examiner can normally be reached M-F 7:30 - 5:00pm.
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/C.T./
Examiner, Art Unit 1637
/Jennifer Dunston/Supervisory Patent Examiner, Art Unit 1637
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