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 .
Election/Restrictions
2. Applicant's election with traverse of Group I in the reply filed on April 13, 2026 is acknowledged. The traversal is on the ground(s) that the examination of full scope would not impose a burden. This is not found persuasive because the present application is a national stage entry case and the consideration of burden does not apply.
The requirement is still deemed proper and is therefore made FINAL.
3. The election of species is withdrawn. The full scope of the elected group was searched and examined.
4. Claims 9 and 10 withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected subject matter. Applicant timely traversed the restriction (election) requirement in the reply filed on April 13, 2026.
Priority
5. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
6. The information disclosure statements (dated April 13, 2026 and December 19, 2023 and December 8, 2023) were in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. The statements were considered. Signed copies of form 1449 are enclosed herewith.
Claim Objections
7. Claim 4 objected to because of the following informality. The claim is grammatically incorrect with a linking word/phrase missing before “A is phenyl.”
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 and 8 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, hydrate, polymorph, co-crystal, tautomer, stereoisomer, isotopically labeled derivative 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, a stable isotope derivative, an isomer or a 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, a stable isotope derivative 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.
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.
9. Claims 1-8 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.
The claims refer to isomers, which is defined on page 5 of the specification as compounds with the same molecular formula but different nature or sequence of bonding of their atoms or the spatial arrangement of their atoms. The structural metes and bounds cannot be ascertained for all compounds that contain the same number and type of atoms, but wherein the bonding arrangement of these atoms is not defined. For the purpose of examination, the term of “isomer” was not further examined or searched. Appropriate correction is required.
Conclusion
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/SUN JAE YOO/Primary Examiner, Art Unit 1621
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