DETAILED ACTION
Claims 1-15, 17 and 22-23, submitted 25 February 2026, are pending in the application. Claims 1-13 and 15 are under examination in the instant Office Action. Claims 14, 17 and 22-23 are withdrawn.
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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-13 and 15, and the elected species,
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, in the reply filed on 25 February 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 14, 17, and 22-23 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 25 February 2026.
The Examiner did not find prior art on the elected species, therefore, the elected species is free of the art. As such, the scope of the search was expanded to include the broader genus.
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.
Claims 1-13 and 15 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 pharmaceutically acceptable salt and solvate variants thereof, does not reasonably provide enablement for wherein the variant is a 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 use the invention commensurate in scope with these claims.
Breadth of the Claims
Claim 1 recites “A compound of formula (I): or a pharmaceutically acceptable salt, solvate, or prodrug thereof...” . The instant claim is not drawn to any prodrug in particular, thus can be interpreted to encompass all prodrugs.
Nature of the Invention
The nature of the invention is within the pharmaceutical arts with regards to a compound of formula (I), a salt, solvate, or prodrug thereof.
State of the Prior Art
The state of the prior art is what one skilled in the art would have known, at the
time the application was filed, about the subject matter to which the claimed invention pertains. The relative skill of those in the art refers to those in the art at the time the
application was filed. See MPEP 2164.05(b). See Pac. Bioscience of Cal., Inc. v. Oxford
Nanopore Techs., Inc., 996 F.3d 1342, 1352, 2021 USPQ2d 519 (Fed. Cir. 2021).
The state of the prior art provides evidence for the degree of predictability in the
art and is related to the amount of direction or guidance needed in the specification as
filed to meet the enabled requirement. The state of the prior art is also related to the
need for working examples in the specification. See MPEP 2165.05(a).
Wankhede et al. ("Challenges and strategies in prodrug design: a comprehensive review." Journal of Advanced Scientific Research 16.06 (2025): 1-20.) teaches a variety of strategies and challenges associated with prodrug design. With regards to drugs reaching the central nervous system, specialized strategies are required to permeate the blood-brain barrier (pg. 2, Section “Facilitating blood-brain barrier (BBB) penetration”, Right Col., 1st paragraph). Wankhede goes on to teach that “The development of CNS-targeted prodrugs is particularly challenging due to the restrictive nature of the blood-brain barrier (BBB)” (pg. 15, Section “CNS Prodrugs”, Right Col., 1st paragraph). Of the challenges associated with prodrug design, Wankhede states that “A critical challenge in prodrug synthesis lies in maintaining orthogonality in deprotection. Each protective group must be removable under distinct conditions without disrupting ester, amide, or carbamate linkages, which are often crucial for prodrug activation.” (pg. 4, Section “Protection Group Strategies”, Right Col., 2nd paragraph). Further challenges associated with prodrug design are selective esterification, maintaining stereochemical integrity, achieving site-specific activation, stability challenges, and pH-dependent hydrolysis (pages 4-5, Section “Linkage Chemistry”, Right and Left Col.).
Geaneotes et al. ("Strategy‐Level Prodrug Synthesis." Chemistry–A European Journal 31.33 (2025): e202501115.) teaches strategies of prodrug synthesis. More specifically, Geaneotes teaches that “FDA-approved prodrugs heavily rely on only a limited subset of the reported methods. Approximately 94% of FDA-approved prodrugs rely on enzymatic prodrug cleavage to an AMA, while 5% are pH-based, and 1% are glutathione-based. Although FDA-approved drugs are limited in their cleavage mechanisms, they achieve a wide range of specific goals, such as improving bioavailability through increasing permeability, solubility, or tracking (53%), achieving targeted delivery (21%), modulating duration of action (14%), mitigating toxicity (6%), enhancing stability (5%), or promoting synergistic effects (1%)” (pg. 1, Section “Introduction”, Right Col., 2nd paragraph).
Finally, Rautio et al. ("The expanding role of prodrugs in contemporary drug design and development." Nature reviews drug discovery 17.8 (2018): 559-587.) teaches the challenges associated with prodrug design and development. Rautio states “Though great progress has been made to characterize prodrugs, the limitations of the different approaches should be carefully considered with respect to the uncertainty in translation to humans. The development of prodrugs is, in general, much more complex and less predictable in the clinic than that of other drugs” (pg. 578, Section “Prodrug challenges and considerations”, Right Col., 1st paragraph). This reference also provided a bullet-point list, Box 3, shown below, which broadly list additional reasons that prodrug synthesis is associated with unpredictability and further points to the uncertainty of the claimed class of prodrugs due to the lack of Examples in the present disclosure detailing the synthesis of said compounds.
Box 3 taught by Rautio
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(pg. 579, top of page)
Level of Skill in the Art
The person of ordinary skill in the art is a person who is presumed to have known
the relevant art at the relevant time. Factors that may be considered in determining the
level of ordinary skill in the art may include: (A) "type of problems encountered in the
art;" (B) "prior art solutions to those problems;" (C) "rapidity with which innovations aremade;" (D) "sophistication of the technology; and" (E) "educational level of active
workers in the field. In a given case, every factor may not be present, and one or more
factors may predominate." In re GPAC, 57 F.3d 1573, 1579, 35 USPQ2d 1116, 1121
(Fed. Cir. 1995); Custom Accessories, Inc. v. Jeffrey-Allan Indus., Inc., 807 F.2d 955,
962, 1 USPQ2d 1196, 1201 (Fed. Cir. 1986); Environmental Designs, Ltd. V. Union Oil
Co., 713 F.2d 693, 696, 218 USPQ 865, 868 (Fed. Cir. 1983). See MPEP 2141.03 (I).
The invention described pertains to the medical or pharmaceutical arts. One of
ordinary skill would be trained in pharmacology, biochemistry, medicine, or a related art
field with a Ph. D or other advanced degree in these or other related fields.
Level of Predictability in the Art
The amount of guidance or direction needed to enable the invention is inversely
related to the amount of knowledge in the state of the art as well as the predictability of
the art. In re Fisher, 427, F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount
of guidance or direction” refers to that information in the application, as originally filed,
that teaches exactly how to make or use the invention. The more that is known in the
prior art about the nature of the invention, how to make, and how to use the invention,
and the more predictable the art is, the less information needs to be explicitly stated in
the specification. In contrast, if little is known in the prior art about the nature of the
invention and the art in unpredictable, the specification would need more detail as to
how to make and use the invention in order to be enabling. The scope of the required
enablement varies inversely with the degree of predictability involved, but even in
unpredictable art, a disclosure of every operable species is not required. A single
embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements. In re Vickers, 141 F.2d 522, 526-27, 61 USPQ
122, 127 (CCPA 1944); In re Cook, 439 F.2d 730, 734, 169 USPQ 298, 301 (CCPA
1971). However, in applications directed to inventions in arts where the results are
unpredictable, the disclosure of a single species usually does not provide an adequate
basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA
1938). In cases involving unpredictable factors, such as most chemical reactions and
physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166
USPQ 18, 24 (CCPA 1970). See MPEP 2164.03. The applicant would need to provide
more objective evidence to support the enablement of the aforementioned claims to
contrast the unpredictability of the subject matter art.
There is unpredictability in the field of endeavor in regards to the currently claimed method of all prodrug variants of compounds of formula (I). The unpredictability stems from prior art teaching the complexity and challenges associated with prodrug design and synthesis.
Amount of Direction Provided by the Inventor
The amount of direction provided by the inventor is correlated by the nature of
the unpredictability of the art. Given the context and scope of the claims mentioned
above, the inventor failed to provide the necessary amount of direction for one skilled in
the art to adequately use the invention across all suggested utility in the broadly stated
disease and disorders disclosed above. (See: Section (A) Breadth of the Claims).
The Applicant provided certain aspect of the instantly claimed invention. For example, guidance was provided on the synthesis of compounds of formula (I) wherein the variant is a salt, found in Example 138d and a solvate, found in Example 79. The instant disclosure fails to discuss any synthesis of a prodrug thereof and as such, the Applicants are not entitled to any and all known or unknown prodrugs of compounds of formula (I).
Quantity of Experimentation Needed to Make or Use the Invention Based on the Content of the Disclosure
As previously stated, the amount of experimentation depends on the art, the
predictability of the art, and the direction provided by the inventor. For one skilled in the
art to practice the invention as disclosed, the artisan trying to practice Applicant’s
claimed invention would be required to undertake unduly burdensome activities
including:
Experimentation to show the synthesis of compounds of the application wherein the compounds are prodrugs of a compounds of formula (I).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Currently, the first 9 compounds listed in dependent claim 11 are drawn to compounds that do not meet the criteria of instant claim 1. The compounds are specifically drawn to compounds of formula (I) wherein the “m” moiety is 0 or 1. Instant claim 1 recites the limitation wherein “m” is 2, 3, 4, or 5”. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements. 35 U.S.C. 112(d) states a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JUSTIN CHRISTOPHER SANCHEZ whose telephone number is (703)756-5336. The examiner can normally be reached Monday -Friday (0730-1700).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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JUSTIN CHRISTOPHER SANCHEZ
Examiner
Art Unit 1622
/J.C.S./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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