DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. 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
2. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 12, 2026 has been entered.
Response to Amendment
3. The declaration under 37 CFR 1.132 filed April 15, 2026 is sufficient to overcome the rejection of claims 1, 4, 14, 15, 17, 18, 24 and 28 based upon RN 2249722-90-3.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
8. Claims 1, 4, 12, 14-19, 21, 23, 24 and 28 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 compounds or the pharmaceutically acceptable salt, solvate, N-oxide, tautomer, stereoisomer or polymorph thereof, does not reasonably provide enablement for the prodrug thereof. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The standard for determining whether the specification meets the enablement requirement was cast in the Supreme Court decision of Mineral Separation v. Hyde, 242 ITS, 261,270 (1918) which postured the question: is the experimentation needed to practice the invention undue or unreasonable? That standard is still the one to be applied, in re Wands, 858 F.2d 731, 737, 8USPQ2s 1400, 1404 (Fed. Cir. 1988). MPEP 2184.01(a) states “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.” The factors are applied below to the instant claims.
The breadth of the claims and nature of invention
The claims are drawn to compounds of Formula (I) or a pharmaceutically acceptable salt, solvate, N-oxide, tautomer, stereoisomer or polymorph, or prodrug thereof.
The state of the prior art, level of ordinary skill, level of predictability, amount of guidance provided
The state of the art and present specification provide guidance on how to make and use pharmaceutically acceptable salt, solvate, N-oxide, tautomer, stereoisomer or polymorph of the claimed compounds. However, neither the specification nor the state of the art provide specific guidance on how to predict and design prodrugs of the claimed compounds including what structural modifications result in these prodrugs.
Furthermore, the state of the art for designing prodrugs is unpredictable and challenging because structural modifications do not have a predictable effect on properties such as absorption, distribution, metabolism excretion or toxicity (ADMET).
“On the basis of this analysis, we discuss strengths and limitations of current prodrug approaches and suggest areas for future development.” Abstract
“As these modifications are likely to affect the physicochemical properties of the prodrug differently, we further investigated whether the distribution of the promoieties would differ depending on the purpose of the prodrug.” Fralish page 369, 1st column, second paragraph
“Release can be further impacted by the mode of administration; for example, through release by gastric enzymes or microbes in oral delivery....” Fralish, page 373, columns 1-2
“Granted, the prodrug approach adds considerable complexity to the molecular design and requires additional safety evaluations for not only the prodrug and the API, but all degradation products. Consequently, prodrug design has historically focused on overcoming ADMET issues...” Fralish, page 379, 1st column
Serendipity has a significant role in the design and careful optimization must be conducted to address each individual drug separately, vs. generic known structural modifications that yield predictable results.
“More recently, although there has been an immense gain in knowledge and a push for the rational design of more complex prodrugs, serendipity still often has a significant role during prodrug design.” Fralish, page 371, Box 1
“Conversely, small-molecule prodrugs are often easy to synthesize, purify, distribute and administer but can be more difficult to design because multi-objective optimization of synthesizability and ADMET properties is required for each project.” Fralish page 366, 1st column, second paragraph
The quantity of experimentation needed to make or use the invention
In the absence of working examples/direction, enablement rests on the existence of an art recognized predictable correlation. Evidence suggests that this requirement is not met for the present case. The amount of experimentation is undue. The experimentation required is to test all structural modifications of the claimed compounds and optimize the modifications relative to parameters such as ADMET in order to determine which modifications result in prodrugs of the claimed compounds. Furthermore, these tests will have to indicate that the modifications produce a prodrug of each of the claimed compounds. It is therefore determined that the present disclosure does not enable one of ordinary skill to practice the scope of the claimed invention.
Conclusion
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/SUN JAE YOO/Primary Examiner, Art Unit 1621
