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 .
Election/Restrictions
Applicant’s election without traverse Group I (drawn to a method for treating Age-related
cognitive impairment in a subject in need thereof), in the reply filed on 11/24/2025 is acknowledged.
Claims 1-16 are pending of which, claims 8-14 and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected INVENTION, there being no allowable generic or linking claim. The restriction requirement is still deemed proper and is made Final.
Pending claims 1-7 and 15 have been examined on the merits.
Claim Rejections - 35 USC § 112 (Written Description)
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 1-7 and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
In Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane), the Federal Circuit noted the importance of an application's disclosure and stated, "the hallmark of written description is disclosure." A disclosure adequately describes an invention when it "reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Id. at 1351. "A 'mere wish or plan' for obtaining the claimed invention is not adequate written description." Centocor Ortho Biotech, Inc. v. Abbott Labs, 636 F.3d 1341, 1348 (Fed. Cir. 2011).
What is required to meet the written description requirement "varies with the nature and
scope of the invention at issue, and with the scientific and technologic knowledge already in
existence." Capon v. Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). The Federal Circuit
explained what is required to meet the written description requirement in Ariad Pharm., Inc. v.
Eli Lilly & Co.:
This inquiry, as we have long held, is a question of fact. Ralston Purina, 772 F.2d
at 575. Thus, we have recognized that determining whether a patent complies
with the written description requirement will necessarily vary depending on the
context. Capon v. Eshhar, 418 F .3d 1349, 1357-58 (Fed. Cir. 2005). Specifically,
the level of detail required to satisfy the written description requirement varies
depending on the nature and scope of the claims and on the complexity and
predictability of the relevant technology. Id. For generic claims, we have set forth
a number of factors for evaluating the adequacy of the disclosure, including "the
existing knowledge in the particular field, the extent and content of the prior art, the
maturity of the science or technology, [and] the predictability of the aspect at
issue." Id. at 1359.
A written description of a chemical genus "requires a precise definition, such as by
structure, formula, [or] chemical name" of the claimed subject matter sufficient to distinguish it
from other materials. Regents of the Univ. of Cal. v. Eli Lilly & Co., 199 F.3d 1559, 1568 (Fed.
Cir. 1997). The Federal Circuit reflected on Eli Lil/yin Ariadwhile explaining how to sufficiently
describe of a genus of compounds:
We held that a sufficient description of a genus instead requires the disclosure of
either a representative number of species falling within the scope of the genus or
structural features common to the members of the genus so that one of skill in the art
can "visualize or recognize" the members of the genus. Id. at 1568-69. We explained
that an adequate written description requires a precise definition, such as by structure,
formula, chemical name, physical properties, or other properties, of species falling within
the genus sufficient to distinguish the genus from other materials. Id. at 1568 (quoting
Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993)). We have also held that functional
claim language can meet the written description requirement when the art has
established a correlation between structure and function. See Enzo, 323 F .3d at 964
(quoting 66 Fed. Reg. 1099 (Jan. 5, 2001). But merely drawing a fence around the outer
limits of a purported genus is not an adequate substitute for describing a variety of
materials constituting the genus and showing that one has invented age nus and not just
a species.
A "representative number of species" must typify the entire claimed genus and account
for variation between the species of the genus.
[A] patentee of a biotechnological invention cannot necessarily claim a genus after only
describing a limited number of species because there may be unpredictability in the
results obtained from species other than those specifically enumerated. Noelle v.
Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004).
Claim 1 recites compounds of Formula (I), wherein substituents are selected from a set of chemical groups. The size of this genus of claimed compounds may be roughly determined by cumulatively multiplying the number of possibilities, n, for each possible substitution around the rings, specifically at the R1, R2, R3, R4, R5, and R6:
(#permutations at R1) x (#permutations at R2) x (#permutations at R3) x (#permutations at (R4) x (#permutations at R5) x (#permutations at R6) x = Total compounds
Taking the R1-R3, as an example, the number of possible substitutions is not limited, thus, a conservative estimate of the number of possible substitutions would be in the thousands
(103) at a minimum. It is important to highlight that each of the R2, R3, R4, R5, and R6 may also be substituted in the same manner. Inserting these estimates into the equation results in billions (1012) of compounds making up the claimed genus.
By contrast to billions of claimed compounds, the specification provides very few species
of compounds typifying the claimed genus. For example, the specification (page 10-11) only depicts about one species with very little variation at R1, R2, R3, R4, R5, and R6, i.e., R1 and R2 are linked together to form a seven membered ring or heptacyclic; R3, R4, and R5 are hydrogen; and R6 is sulfamate. The one species of as presented in the specification and claims 5 and 6 offered to support the genus of billions of compounds account for very little variation as compared to the claimed genus. Therefore, compound STX64 as supporting species, clearly lacks variation among the substituents, cannot possibly account for the variability found across a genus that encompasses billions of compounds.
Chemistry is generally considered to be unpredictable and/or have unpredictable factors.
See, e.g., ln re Carleton, 599 F.2d 1021, 202 USPQ 165,170 (CCPA 1979) ("Although there is a
vast amount of knowledge about general relationships in the chemical arts, chemistry is still
largely empirical, and there is often great difficulty in predicting precisely how a given compound will behave."). The pharmaceutical arts, that is the use of a chemical compound to affect a desired physiological activity, is generally considered to be unpredictable and/or have
unpredictable factors. See, e.g., In re Fisher, 427 F.2d 833, 839 (CCPA 1970) ("In cases
involving unpredictable factors, such as most chemical reactions and physiological activity, the
scope of enablement obviously varies inversely with the degree of unpredictability of the factors
involved (emphasis added); In re Bowden, 183 F.2d 115, 86 USPQ 419, 423 ("chemical reactions frequently are unpredictable").
Considering the unpredictability found in organic synthesis, exchanging even one
substituent for another cannot be considered a foregone conclusion. Accordingly, when a claim
presents a genus with substantial variation as that currently presented by claims 1, and 5-6, the disclosure must adequately reflect such variation with a representative number of species.
The lack of any disclosure of examples may be considered in determining whether a claimed invention was adequately described. Boston Scientific Corp. v. Johnson & Johnson, 647 F.3d
1353 (Fed. Cir. 2011).
As is the case here, very few examples do not provide a "representative number of
species" for an unpredictable art such as a chemistry. See, e.g., Ariad, 598 F.3d at 1354-55
(claiming that the inventor has an obligation to disclose examples when the art is unpredictable).
The specification, then, is considered devoid of sufficiently detailed, relevant, identifying
characteristics demonstrating that Applicant was in possession of the entirety of the genus now
claimed, i.e., additional complete or partial structures, other physical and/or chemical properties,
functional characteristics coupled with a known or disclosed correlation between function and
structure, or some combination thereof demonstrating possession of the entirety of the claimed
genus.
Epitestosterone Sulfate (ES)
Epitestosterone sulfate (ES) is a natural steroid molecule, and the specification fails to disclose how ES is obtained, or whether the compound was synthesized, or purchased, or otherwise made available for use in the claimed method. The specification merely disclosed ES as a tested a compound without providing any preparation methods, or enabling guidance. Moreover, the claim encompasses ES “salts or esters,” yet the specification contains no description, examples, structural information, or teaching enabling a POSITA to identify, prepare, or use any such salts or esters. Moreover, given that epitestosterone is an uncharged steroid molecule, therefore any salt or ester form of the compound is important to disclose, because such information is critical for analysis, such as solubility. For these reasons, while specification demonstrates possession of ES, however, the specification does not establish possession across the full scope claimed any salts or esters. This further supports the conclusion that the specification lacks adequate written description of the claimed subject matter.
Method For Treating Age-Related Cognitive Impairment
The specification (page 30-36) describes, including but not limited to motor ability, Y-maze test, short/long-term memory assays, using murine data reflecting improvement in cognitive deficits associated with cognitive impairment such as Mild Cognitive Impairment (MCI), Age-Associated Memory Impairment (AAMI), or Age-Related Cognitive Decline (ARCD). However, the models do not provide detailed guidance or representative data for the full scope of the claimed genus, “Age-related cognitive impairment,” which to include additional clinically recognized subsets such as cognitive impairment-no dementia (CIND) and other heterogenous age-related cognitive disorders. The specification contains no description, examples, models, biomarkers, or functional evidence demonstrating that Applicant are in possession of treatment for these broader subsets, or does specification provide a rational supporting applicability beyond the specifically tested forms of cognitive decline. Moreover, the specification fails to mention whether the same method of treatment (e.g., doses, formulations or treatment regimens) is applicable across the various subtypes of age-related cognitive impairment, including but not limited to Lewy Body Dementia (LBD), and Frontotemporal Dementia (FTD). In addition, given that age-related cognitive impairment manifests differently in males and females, as evidence by Levine (page 8-9):
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These differences between gender strongly suggest that treatment efficacy and safety may vary between the gender groups, making it essential to include both gender in the preclinical studies. Furthermore, while animal models provide valuable preclinical data, they are not sufficient by themselves to claim a therapeutic treatment for age-related cognitive impairment in a human subject, because of the complexity of the disease. Therefore, not only the specification fails to disclose the gender of the animals used in the studies, but also no humans were included in the studies. (Levine et al., JAMA Netw Open. 2021;4(2):e210169). While mouse study provides early therapeutic evidence for a treatment, but because translation often fails due to biological differences, and disease manifestation, therefore, it is evident that a POSITA would require that treatment approach for age-related cognitive impairment to involve human clinical trials for validation. This further supports the conclusion that the specification lacks adequate written description of the claimed subject matter.
Furthermore, regarding a composition comprising “at least one of epitestosterone sulfate
(ES), or any salts or esters thereof, and compounds capable of inhibiting the steroid
sulfatase of Formula (I);” Figure 20 and 21 of the specification disclose results for open field, Y-maze, and learning and memory, using either the individual, (STX or ET-S) compounds or the combination (STX + ET-S). However, the data, as reflected in the bar graph heights and overlapping error bars, indicate no apparent significant improvement for the combined compound compared to the individual group. In particular, the Y-maze, and learning and memory results show that ET-S or STX64 alone produce effects comparable to the combination, suggesting no additive or synergistic benefits from combining the compounds. The specification clearly fails to provide any guidance or evidence that administering the combination offers a greater benefit to a subject in need thereof than administering either compound alone. Therefore, given that animal-based Y-maze, learning and memory tests which are widely recognized in the art as part of the standard models for evaluating therapeutic efficacy in age-related cognitive impairment, the lack of demonstrated advantage of the combined treatment do raise substantial question regarding its application as a method of treatment over the individual compound alone. This is because, according to Ruiz (abstract, page 1, [0008]) teaches steroid sulfatase enzyme STX64 for the treatment of ageing, including but not limited to dementia and Alzheimer’s disease). Thus, the fact the specification fails to highlight the explicit benefit of the claimed composition in view of Figure 20 and 21, this indicates that the scope of the claimed invention unsupported and indefinite. This further supports the conclusion that the specification lacks adequate written description of the claimed subject matter.
All other claims depend directly or indirectly from the rejected claims and are, therefore, also rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, for the reasons set forth above.
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.
Claim 1 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.
Claim 1 recites the phrase “compounds capable of inhibiting the steroid sulfatase of Formula (I)” from the text below:
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The phrase “capable of inhibiting the steroid sulfatase of Formula (I)” is vague without specifying the exact conditions, such as assay parameters, or structural features that would allow a POSITA to determine whether a compound satisfies the claim limitation. Therefore, it is unclear whether the inhibition relies on the compound itself or on external factors such as enzyme oxidation state, concentration, or tissue environment. This ambiguity can lead to confusion regarding the specific action intended by the claim.
Two or more of Rl-R6 are Linked Together
Claims 1 recites “two or more of Rl-R6 are linked together,” without clearly identifying the substituents of group from which the substituents are to be selected. The specification does not provide any description, examples, or definitions clarifying the identity, scope, or chemical nature of the substituents or the selection list; which renders the claims indefinite.
Insufficient Antecedent
Claim 1 recites the limitation “the group consisting of at least one of epitestosterone sulfate” in the third line of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claims 5 and 6 recite the limitation “the sulfatase inhibitor STX64 of Formula (II)” in the second line of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Objections
The specification and drawings inconsistently refer to epitestosterone sulfate using multiple abbreviation, “ES”, “E-S” and “ET-S” as disclosed in the specification (page 8; drawings, Figure 20 and 21), as an example. Such inconsistency would create confusion within the text, and may lead to ambiguity regarding the claimed compound. For clarity, Applicant is advised to select one of the abbreviations, and remove any alternative notation.
Subject Matter Free of the Art of Record
The subject matter of claim 1 is free of the art of record. The closest prior art is Ruiz et al., US20160361244 A1. While Ruiz teaches “steroid sulfatase enzyme STX64 for the
treatment of ageing and, therefore, to increase the longevity of individuals or improve their quality of life,” however there is no motivation for an ordinary skill in the art to modify the teaching of Ruiz, by combining STX64 with “epitestosterone sulfate (ES), or any salts or esters thereof,” to arrive at the claimed compound. The claims 1-7 and 15 are not allowed because of the issues indicated above. As a result, until this issue is remedied or resolved; the claims cannot be subject of allowance.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST).
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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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/P.P.E./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622