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 .
Priority
The present application U.S. Appln. Ser. No.: 18/001,190, Filed: December 08, 2022 is a 371 Nat. Stage Entry of WO 2021/252691 A1 (i.e., PCT/US2021/036692, Intern.’l Filing Date: June 9, 2021, Intern.’l Pub. Date: December 16, 2021), which claims priority from U.S. Prov. Appln. No.: 63/037,470, Filed: June 10, 2020.
Status
This is in response to the May 2, 2025 Information Disclosure Statement in the above-identified application.
Claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 61-62, 69 and 73 are pending and amended and claims 3-4, 6-8, 10-11, 14-15, 17-19, 21-25, 27, 30-31, 33-39, 41-48, 51-54, 56-60, 63-68, 70-72 and 74-78 are cancelled in the above identified application.
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on May 2, 2025, August 19, 2024 and July 11, 2022 is in compliance with the provisions of 37 CFR 1.97.
Accordingly, Information Disclosure Statements have been considered by the Examiner.
Specification
[a] The abstract of the disclosure is objected to because:
The abstract of the disclosure lacks specificity in defining the proper content of claimed invention. For example, in chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
The abstract of the disclosure does not commence on a separate sheet in accordance with 37 CFR 1.52(b)(4) and 1.72(b).
A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
[b] The specification has not been checked to the extent necessary to determine the presence of all possible errors .
Applicants’ cooperation is required in correcting any errors of which applicants are aware of in the specification. MPEP § 608.01.
Claim Objections
Claims 8 is objected to because of the following informalities: there indefinite articles are missing before elements defined in this claim as follows:
“The method of claim 1, wherein a delta opioid receptor (DOR) antagonist comprises a RNAi; a small molecule; a peptide; a protein; or an antibody that targets the delta opioid receptor”.
Appropriate correction is required accordingly.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 61-62, 69 and 73 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd para., 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 Applicants), regards as the invention.
In general, the claims of the present invention fail to define the metes and bounds of the claimed invention due to use of indefinite, vague, ambiguous or unclear or poorly defined functional terms and/or language (i.e., such that exact scope of the claimed invention cannot be ascertained) without support from the specification within the claim itself. Claims must particularly point out and distinctly the claimed invention. Moreover, claims identified above also lack clarity, due to unnecessary use of repetitive and/or redundant terms.
[1] The following groups:
[A] claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55 and 61 ; and
pharmaceutical composition claim 62, respectively, are rejected for lacking clarity and for being vague, ambiguous and indefinite for recitation of the phrase “optionally substituted thereof” associated with specific and different individual variables and/or functional groups in the instant claims, i.e., e.g.,
except it is unclear exactly what optional substituent groups are actually substitutable on each specific variable/functional groups as defined within the context the claimed invention.
[B] method claims 69 and 73 are rejected for same reasons supra
for recitation of the phrase “or any pharmaceutically acceptable salt, isotopically labeled variant or solvate thereof”.
A person of ordinary skill in the art would not be able to determine with reasonable certainty what the metes and bounds of the claimed invention are, because:
aforementioned claims set forth very broad terms (i.e., such as “ANY” in claim 69) and without specific boundary limiting definitions i.e., e.g.,
“optionally substituted” after various functional groups defined therein, it is unclear what functional groups are optionally substituted with, clarification is requested inclusion with functional group definitions from the specification would be helpful.
Amendment of the claims to delete the above-identified phrases is required accordingly
[2] appears before the first recitation of each term “atoms” and “structure” as it relates to each new cyclic ring structure formed ; i.e., e.g., where each Rx or Ry may be selected from R2, R3, R2a, R2b, R3a, R3b, R4a, R4b, R5a, and R5b etc.); and
[B] Further, claim 1 recites the phrase
“or two of R4-R7 are taken together with the atoms to which they are attached to form an optionally substituted 5- or 6-membered ring (e.g.. cycloalkyl or heterocycloalkyl)”; i.e., it is unclear what constitutes “two of R4-R7” as it is not spelled out, clarification is requested. A suggested amendment is two of variables selected from any of R4, R5, R6, or R7", such as two variables selected;
where each phrase renders claim 1 indefinite.
[3] Claim 69 recites the phrase “or any pharmaceutically acceptable salt, isotopically labeled variant or solvate(s) thereof
Based on the foregoing with regard to [1] to [3] supra, appropriate correction and amendment is required accordingly.
Claim Rejections - 35 USC § 112(a)
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 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 61-62, 69 and 73 are rejected under 35 U.S.C. 112(a), because the specification, while enabling for:
[A] A compound as exemplified by structures shown of:
Formula (II-A’)
PNG
media_image1.png
144
223
media_image1.png
Greyscale
or
PNG
media_image2.png
153
287
media_image2.png
Greyscale
; or
Formula (IB):
[AltContent: textbox (or)]
PNG
media_image3.png
140
250
media_image3.png
Greyscale
or
PNG
media_image4.png
237
783
media_image4.png
Greyscale
; respectively, or
a pharmaceutically acceptable salt thereof; and
where:
Examples 1-13 and 16-30 exemplify compounds of (a); and
Examples 14 and 15 exemplify compounds of (b), respectively;
i.e., see specification at paras [0475] to[0563]; and
[B] corresponding pharmaceutical composition(s) thereof (i.e., as defined in A above);
IT DOES NOT REASONABLY PROVIDE ENABLEMENT FOR CLAIMED/ELECTED INVENTION AS SET FORTH BELOW, which are comprised of:
ALL compounds encompassed by the generic Formula (I) or a pharmaceutically acceptable, ALL or ANY isotopically labeled variant(s) or ALL or ANY solvate(s) thereof of a compound of Formula (I) or a pharmaceutically acceptable salt thereof (i.e., as defined in claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 61-62, 69 and 73)
A method for treating ALL or ANY neurological disease(s) or disorder(s) in ALL or ANY mammal(s), the method comprising administering to ALL or ANY mammal(s),
a compound of claim 1, or ALL or ANY pharmaceutical acceptable salt(s), ALL or ANY isotopically labeled variant(s) or ALL or ANY solvate(s) thereof (i.e., as in claim 63)
The method of claim 69, wherein ALL or ANY neurological disease(s) or disorder(s) is/are selected from the group consisting of:
Alzheimer's disease, Parkinson's disease, Huntington's disease, a phobia, brain cancer, depression, treatment resistant depression, obsessive compulsive disorder (OCD), dependence, addiction, anxiety, post-traumatic stress disorder (PTSD), suicidal ideation, major depressive disorder, bipolar disorder, schizophrenia, stroke, and traumatic brain injury.(i.e., as in claims 69 and 73)
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
Amount Of Guidance Provided By Applicant and 3. Number of Working Examples.
The instant specification generally teaches:
[A] compounds of Formula (I):
PNG
media_image5.png
272
346
media_image5.png
Greyscale
(I); or a pharmaceutically acceptable salt(s) thereof; and
a corresponding pharmaceutical composition thereof.; and
[B] under the specification section entitled “BIOLOGICAL EXAMPLES” limited solely to invitro assays directed to:
“Hallucinogenic Potential” demonstrating dose-dependent head-twitch response in mice . . .; and
other miscellaneous preliminary pre-clinical assays (i.e., such as receptor assay and other fundamental screening studies, etc.) which do not indicate what, if any neurological diseases and/or disorders could be treated by the compounds of Formula (I) or a pharmaceutically acceptable salt, isotopically labelled variants or solvates thereof (i.e., see specification at (from paras. [0580] to [0619])
Other than that summarized above, in the specification:
there are NO WORKING EXAMPLES directed to:
ALL compounds encompassed by Formula (I) or a pharmaceutically acceptable salt, isotopically labeled variant(s) or solvate(s) thereof;
use of any identified compounds as treatment neurological diseases or disorders and the like,
other than for example,
compound Examples 1-30 exemplify specific compounds identified supra; i.e., see structures above and specification at paras [0475] to[0563]; and
assays such as:
an vitro Serotonin 5-HT2A and 5-HT2C in vitro radioligand binding and cellular IPOne agonism assays. The binding and agonism functional potencies of the compounds (as indicated by their IC5os or EC50s) are shown in Table 2 (i.e., see paras [0598]);
invitro neurite outgrowth assay, etc.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
Regarding information above, the lack of working examples, the ability to claim the broad scope without additional substantive examples cannot be simply willed into existence.
In the instant case, the originally filed disclosure is not sufficient to allow extrapolation of the limited examples to enable treatment of all variants of the overly broad claim directed to “methods for treatment of all neurological diseases or disorders”, which appears to cover more than one invention.
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190:
“The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However, there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.”
The same circumstance appears to be true here. Hence, Applicants must show that the claims as written, other than those exemplified in the present invention and identified in examples can be made and used for the stated purpose, or limit the claims to be commensurate with that which is exemplified accordingly.
The Nature Of The Invention And Predictability In The Art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Scope Of The Claims.
The scope of the claims relates to:
Compounds of Formula (I):
PNG
media_image6.png
221
210
media_image6.png
Greyscale
; or
a pharmaceutically acceptable salt, isotopically labeled variant, or solvate thereof;
A pharmaceutical composition, which comprises a compound of Formula (I) or a pharmaceutically acceptable salt, isotopically labeled variant, or solvate thereof, and at least one pharmaceutically acceptable excipient; and/or
Methods for treating a neurological disease or disorder in a mammal, the method comprising administering to the mammal a compound of claim 1 or any pharmaceutically acceptable salt, isotopically labeled variant, or solvate thereof.
Thus, the scope of claims is very broad.
Nature Of The Invention.
The nature of this invention relates to compounds of Formula (I) or a pharmaceutically acceptable salt, isotopically labeled variant, or solvate thereof, and at least one pharmaceutically acceptable excipient; corresponding pharmaceutical compositions, and methods for promoting neuronal growth and/or improving neuronal structure, treating diseases or disorders that are mediated by the loss of synaptic connectivity and/or plasticity, such as neurological diseases and disorders, with non-hallucinogenic psychoplastogens.
Level Of Skill In The Art.
An ordinary artisan in the area of drug development would have experience in screening chemical compounds for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)." That conclusion is clearly justified here that Applicant is not enabled for making these compounds or compositions or treating the diseases mentioned.
That conclusion is clearly justified here as Applicants are not enabled for making or using all these compounds (i.e., as described in general terms, inc., but not limited to starting materials, intermediates, etc.) or pharmaceutical compositions thereof (i.e., e.g., by using not specifically reagents and/or, reactions conditions, etc. ) or treating the diseases taught in the specification.
Based on the foregoing and U.S. patent law, it is unclear what neurological disease or disorder compounds of the present invention actual treat. The specification only teaches “serotonin and opioid receptor functional assays, with some compound example data indicating binding or agonism activity of In vitro 5-HT2A and 5-HT2C Radioligand Binding and Cellular IPOne Agonism Activity.
Appropriate claim amendments limited to enable scope identified herein, clarification and action is required accordingly in the instant application.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Background of the Present Invention: Relevant to Art Rejections Recited Herein
The present invention relates to a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
PNG
media_image7.png
117
387
media_image7.png
Greyscale
PNG
media_image7.png
117
387
media_image7.png
Greyscale
All Compound Subgenus Encompassed by Formula (I)
PNG
media_image8.png
805
749
media_image8.png
Greyscale
;and
corresponding pharmaceutical compositions, and methods for treatment of as neurological diseases and disorders, with non-hallucinogenic psychoplastogens.
[1] Claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 62, 69 and 73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2011/103433 A1 to Medivation Technologies, Inc. (i.e., Intern.’l Filing Date: February 18, 2011; Intern.’l Pub Date: August 25, 2011; “WO ‘433 Appln").
In general, the WO ‘433 Appln. teaches and discloses pyrido[4,3-b]indole and pyrido[3,4-b]indole compound derivatives of Formula (IA):
PNG
media_image9.png
313
655
media_image9.png
Greyscale
;
corresponding pharmaceutical compositions and treatment methods for a variety of diseases (i.e., inc. neurological diseases and disorders, those associated with neurotransmitter-mediate or neuronal disorders)
In particular, the WO ‘433 Appln. discloses compounds 153-155 therein, which correspond to and anticipates the claimed invention per chemical structures below taught by the claimed invention:
PNG
media_image10.png
262
1193
media_image10.png
Greyscale
[AltContent: textbox ()][AltContent: textbox ()][AltContent: textbox ()]
PNG
media_image11.png
267
889
media_image11.png
Greyscale
PNG
media_image12.png
280
463
media_image12.png
Greyscale
CORRESPONDS TO CLAIMED INVENTION
n = 1; m = 2
R10 = alkyl (methyl)
R7 = substituted alkyl
(w/ aryl, OH, Me)
R6 = N
R5 = alkyl (methyl)
R1 = H
n = 1; m = 2
R10 = alkyl (methyl)
R7 = substituted alkyl
(w/ heteroaryl, OH)
R6 = N
R5 = alkyl (methyl)
R1 = Me
n = 1; m = 3
R10 = alkyl (methyl)
R7 = substituted alkyl
(w/ heteroaryl, OH, Me)
R6 = N
R5 = alkyl (methyl)
R1 = Me
PNG
media_image13.png
321
876
media_image13.png
Greyscale
Therefore, WO ‘433 Appln. anticipates the claimed invention.
[2] Claims 1-2, 5, 9,12-13,16, 20, 26, 28-29, 32, 40, 49-50, 55, 62, 69 and 73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2009/055828 A1 to Medivation Technologies, Inc. (i.e., Intern.’l Filing Date: October 27, 2008; Intern.’l Pub Date: April 30, 2009; “WO ‘828 Appln").
In general, the WO ‘828 Appln. teaches and discloses pyrido[4,3-b]indole and pyrido[3,4-b]indole compound derivatives of Formula (IA):
PNG
media_image14.png
382
391
media_image14.png
Greyscale
;
corresponding pharmaceutical compositions (i.e., see throughout the instant specification, inc. paras. [0016], [0086], [0158], [0279]-[0282] and treatment methods for a variety of diseases (i.e., inc. (i.e., see throughout the instant specification, inc. paras. [0309]-[0325] neurological diseases and disorders, those associated with neurotransmitter-mediate or neuronal disorders, i.e., such as Alzheimer’s and Huntington’s diseases)
In particular, the WO ‘828 Appln. discloses compounds that read on and anticipate the claimed invention, i.e., see specific compounds below from Table 2 and corresponding preparation methods for those in the specification
PNG
media_image15.png
191
326
media_image15.png
Greyscale
PNG
media_image16.png
185
340
media_image16.png
Greyscale
PNG
media_image17.png
112
339
media_image17.png
Greyscale
PNG
media_image17.png
112
339
media_image17.png
Greyscale
PNG
media_image18.png
89
339
media_image18.png
Greyscale
PNG
media_image18.png
89
339
media_image18.png
Greyscale
Therefore, the WO ‘828 Appln. anticipates the claimed invention.
Prior Art Information
Below is the prior art made of record and not relied upon is considered pertinent to applicant's
disclosure:
PNG
media_image19.png
30
541
media_image19.png
Greyscale
PNG
media_image19.png
30
541
media_image19.png
Greyscale
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689. The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicants is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/ Supervisory Patent Examiner, Art Unit 1624