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 .
Status
Claims 1-16 are pending and under examination.
Priority
This application is a continuation of U.S. Application No. 19/209,346, filed May 15, 2025, which is a continuation of U.S. Application No. 18/629,056, filed April 8, 2024, which is a divisional of U.S. Application No. 18/321,266, filed May 22, 2023, which is a bypass continuation of International Application No. PCT/US2023/067057, filed May 16, 2023, which claims the benefit of, and priority to, U.S. Provisional Application No. 63/364,759, filed May 16, 2022.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 7/9/2026 has/have been considered by the Examiner. The submission(s) is/are in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
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.
Scope of Enablement
Rejection maintained, slightly modified to address new amendments:
Claims 1-16 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
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(a.k.a. “SPI-62”, structure in Claim 1) as the HSD-1 inhibitor compound that does not show tachyphylaxis for HSD-1 inhibition, does not reasonably provide enablement for all HSD-1 inhibitor compounds modified by them not showing tachyphylaxis for HSD-1 inhibition and forming ternary complexes with NADPH in the human HSD-1 active site. 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.
The specification does not provide any competent evidence or disclosed tests that are highly predictive for the pharmaceutical use of the instant composition. Pharmacological activity in general is a very unpredictable area. Note that in cases involving physiological activity such as the instant case, "the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved". See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Unpredictability of the art.
HSD1 inhibitors have been used for the treatment of patients with diabetes and glucocorticoid excess but, with repeated dosing, the inhibitors tend to quickly lose effectiveness (i.e., display tachyphylaxis) for inhibiting HSD1 in adipose tissue. (Gutierrez et al. – see IDS) Effectiveness of HSD1 inhibitors is lost within 14 days of repeated doses of the inhibitor (Katz et al. (Annals of the Rheumatic Diseases. Volume 82, Supplement 1, June 2023, Page 208); see IDS). However, Applicant's SPI62 compound does not lead to tachyphylaxis and maintains effectiveness when SPI62 is used in repeated doses to treat patients. (See Fig. 1 of instant application).
The prior art does not teach or suggest SPI62, unlike other HSD1 inhibitors, would maintain efficacy in inhibiting HSD-1 in adipose tissue after repeated doses including other known pseudo-irreversible inhibitors in patients.
In the Katz declaration signed 4/15/2025, SPI-62 was shown to unexpectedly maintain effectiveness after long term use. This was surprising given the fact that other HSD-1 inhibitors lose effectiveness, examples include compounds disclosed in the current specification and previously claimed.
Relative skill of those in the art.
One of ordinary skill in the art is one with access to reagents, tools and equipment used for diagnosing disease, performing tests and/or administering treatment to individuals. The skilled artisan also has many years of training and experience in either the clinical or laboratory environment or both. Therefore, it is clear that the level of skill of one in the art is high. However, this high level of skill is overcome in view of the limited teachings provided by the specification and the unpredictable state of the art, it would require the skilled artisan undue experimentation to make and use the invention commensurate to the scope of the claims.
The breadth of the claims. The breadth of the claims is exacerbated by reading on every HSD-1 inhibitor that forms the recited ternary complex with NADPH in the HSD-1 active site and does not show the recited tachyphylaxis without limitation as to chemical class, scaffold, or substituent composition.
The amount of direction or guidance presented. The specification discloses that only SPI-62 meets the claimed stability of activity of the HSD-1 inhibitor.
In the specs, the Applicant states:
[0039] The present disclosure describes an important type of HSD-1 inhibitors, pseudo-irreversible HSD-1 inhibitors, which have demonstrated a previously unknown advantage for two members of that sub-class, BI-187004 and SPI-62. Unlike certain other HSD-1 inhibitors (e.g., AZD4017, AZD8329, BI-135585), BI-187004 shows limited, and SPI-62 does not show, tachyphylaxis of human adipose HSD-1 inhibition with multiple dosing.
Here, Applicant acknowledges what others have about the well-known tachyphylaxis problem with HSD-1 inhibitors, generally.
The amount of direction or guidance is not adequate enough to enable one of ordinary skill in the art to use any other HSD-1 inhibitor as claimed.
The presence or absence of working examples. As stated above, the specification only adequately discloses SPI-62 as capable to obtained the claimed functional stability. No other member of the genus is shown, by working example, to possess the claimed property.
The quantity of experimentation necessary. Since treating a human with an HSD-inhibitor is known to have problems with tachyphylaxis, a person of ordinary skill in the art cannot predicted a priori that the HSD-1 inhibitors encompassed by the claims would meet the required functional stability. It must be determined in a case-by-case manner by painstaking experimental study and when the above factors are weighed together, one of ordinary skill in the art would be burdened with undue "painstaking experimentation study" to use the invention commensurate in scope with the claims.
Given the analysis of the factors which the courts have determined are critical in determining whether a claimed invention is enabled, it must be concluded that the skilled artisan would have to conduct undue and excess experimentation in order to practice the claimed invention.
Response to arguments
Applicant's arguments have been fully considered but have not been found to be persuasive. Claim 1 has been amended to delete the compound structures and to recite, inter alia, "wherein the HSD-1 inhibitor compound forms ternary complexes with NADPH in the human HSD-1 active site." Applicant asserts this amendment is supported and enabled by the specification. For support, Applicant points to paragraph [0188] in Example 9 and mentions that it states "SPI-62 and certain other HSD-1 inhibitors form ternary complexes with NADPH in the human HSD-1 active site predicts that members of this genus of pseudo-irreversible HSD-1 inhibitors will not show tachyphylaxis on adipose HSD-1 inhibition."
However, as established above, treatment with HSD-1 inhibitors that form a ternary complex and not show tachyphylaxis is unpredictable given that many HSD-1 inhibitors display tachyphylaxis with long-term use. The statement in paragraph [0188] that ternary-complex formation necessarily “predicts” the genus “will not show” tachyphylaxis does not support enablement. The possession of the combination of these properties is only confirmed for SPI-62. There is no data establishing that the recited complex formation is the necessary feature that will provide HSD-1 inhibitors with the lack of tachyphylaxis.
Applicant further identifies 0163 stating that it further provides examples of HSD-1 inhibitors that show tachyphylaxis and do not form ternary complexes that include NADPH.
However, while this may exclude non-members; it does not enable the members encompassed by the claims. And that a artisan could identify that a ternary-complex former does not establish that each achieves the claimed function without undue experimentation.
Therefore, the rejection is deemed to still be proper and is, therefore, maintained.
Written Description
New Rejection, necessitated by amendment:
Claims 1-16 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.
The written description requirement of the patent statute demands a description of the invention itself, not an indication of a result that one might achieve if one made the invention. See, e.g., In re Wilder, 22 USPQ 369, 372-3 (Fed. Cir. 1984). (Holding that a claim was not adequately described because the specification did ‘little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.’)
Mere indistinct terms – here, “HSD-1 inhibitor”, “does not show tachyphylaxis”, “forms ternary complexes with NADPH in human HSD-1 active site” – do not suffice to meet the written description requirement. This is particularly true when a compound is claimed in purely functional terms. See Univ. of Rochester v. G.D. Searle, 69 USPQ2d 1886 (CAFC 2004) at 1892, stating:
The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. A description of an anti-inflammatory steroid, i.e., a steroid (a generic structural term) described even in terms of its functioning of lessening inflammation of tissues fails to distinguish any steroid from others having the same activity or function. A description of what a material does, rather than of what it is, usually does not suffice…. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. (Emphasis added).
For a claimed genus, possession is established by either disclosure of (i) a representative number of species falling within the scope of the genus, or (ii) relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus. See MPEP § 2163.
However, the specification discloses a limited number of species – namely, SPI-62 – for which the claimed property of non-tachyphylactic adipose HSD-1 inhibition with formation of a ternary complex with NADPH in the HSD-1 active site is held and observed. This disclosure is not considered as a representative number of species for the genus claimed. As defined by function, the genus reads on any molecule so classified, without limitation to structure, and therefore, encompasses substantial and divergent variance including agents unrelated by structure, physical, or chemical properties and reaching multiple structural classes, e.g., peptides, complex proteins, prions, small compounds, and more. The limited disclosure cannot support possession of the claimed genus.
Accordingly, the specification does not provide a representative number of useful HSD-1 inhibitors falling within the claims claimed genus, a potentially huge genus inclusive of many different molecules having widely divergent structures and functions. The specification discloses no readily apparent combination of identifying characteristics other than the disclosure of those specific species as examples of the claimed genus.
Applicant can obviate this rejection by limiting the claims to the species having written description support in the as-filed specification, namely, SPI-62.
Terminal Disclaimer
The terminal disclaimer filed on July 9, 2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Application no. 19/446,133; U.S. Application no. 19/446,127; U.S. Application no. 19/446,144; U.S. Application no. 19/446,115 and U.S. Patent No. 12,329,745 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Conclusion
No claims are allowed.
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 CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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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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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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