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 .
Non-Final Rejection
. The Status of Claims:
Claims 1-2, 5, 7-19, 21-22 and 27-28 are pending.
Claims 1-2, 5, 7-19 are rejected.
Claims 21-22 and 27-28 are withdrawn from consideration.
DETAILED ACTION
1. Claims 1-2, 5, 7-19 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/US2021/052163 09/27/2021 , which has a priority of 63084143 09/28/2020.
Drawings
3. The drawings field on 3/28/2023 are accepted by the examiner.
IDS
4. The IDS filed on 3/28/2023 & 9/10/2025 are reviewed by the examiner.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restriction
Applicant’s election without traverse of Group I (claims 1-2, 5, and 7-19 ) on 9/21/26 is acknowledged. Claims 27-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected groups II-III, there being no allowable generic or linking claim.
The elected compound 38 is not allowable
PNG
media_image1.png
149
259
media_image1.png
Greyscale
.
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 1-2, 5 and 7-19 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for making salts of the claimed compounds, does not reasonably provide enablement for making solvates of the claimed compounds. The specification does not enable any person skilled in the art of synthetic organic chemistry to make the invention commensurate in scope with these claims. “The factors to be considered [in making an enablement rejection] have been summarized as a) the quantity of experimentation necessary, b) the amount of direction or guidance presented, c) the presence or absence of working examples, d) the nature of the invention, e) the state of the prior art, f) the relative skill of those in that art, g) the predictability or unpredictability of the art, h) and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. In the present case the important factors leading to a conclusion of undue experimentation are the absence of any working example of a formed solvate, the lack of predictability in the art, and the broad scope of the claims.
c) There is no working example of any solvate formed. These cannot be simply willed into existence. 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. There is no evidence that solvates of these compounds actually exist; if they did, they would have formed. Hence, applicants must show that solvates can be made, or limit the claims accordingly.
g) The state of the art is that is not predictable whether solvates will form or what their composition will be. In the language of the physical chemist, a solvate of organic molecule is an interstitial solid solution. This phrase is defined in the second paragraph on page 358 of West (Solid State Chemistry). West, Anthony R., "Solid State Chemistry and its Applications, Wiley, New York, 1988, pages 358 & 365. The solvent molecule is a species introduced into the crystal and no part of the organic host molecule is left out or replaced. In the first paragraph on page 365, West (Solid State Chemistry) says, “it is not usually possible to predict whether solid solutions will form, or if they do form what is their compositional extent". Thus, in the absence of experimentation one cannot predict if a particular solvent will solvate any particular crystal. One cannot predict the stoichiometery of the formed solvate, i.e. if one, two, or a half a molecule of solvent added per molecule of host. In the same paragraph on page 365 West (Solid State Chemistry) explains that it is possible to make meta-stable non-equilibrium solvates, further clouding what Applicants mean by the word solvate. Compared with polymorphs, there is an additional degree of freedom to solvates, which means a different solvent or even the moisture of the air that might change the stabile region of the solvate.
h) The breadth of the claims includes all of the hundreds of thousands of compounds of formula (I). Thus, the scope is broad.
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. Thus, undue experimentation will be required to practice Applicants' invention.
Claim 19 is rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for treating specific diseases by an additional therapeutic agent, does not reasonably provide enablement for preventing a neurologic al disease or disorder . 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. Applicants are not enabled for preventing the neurologic al disease or disorder. The only established prophylactics are vaccines not the additional therapeutic agent such as present here. In addition, it is presumed that “prevention” of the claimed diseases would require a method of identifying those individuals who will develop the claimed diseases before they exhibit symptoms. There is no evidence of record that would guide the skilled clinician to identify those who have the potential of becoming afflicted.
“The factors to be considered [in making an enablement rejection] have been summarized as the quantity of experimentation necessary, the amount of direction or guidance presented, the presence or absence of working examples, the nature of the invention, the state of the prior art, the relative skill of those in that art, the predictability or unpredictability of the art, and the breadth of the claims”, In re Rainer, 146 USPQ 218 (1965); In re Colianni, 195 USPQ 150, Ex parte Formal, 230 USPQ 546. 1) As discussed above, preventing diseases requires identifying those patients who will acquire the disease before chronic and acute pain occurs. This would require extensive and potentially opened ended clinical research on healthy subjects. 2) The passages from line 3 to line 5 on page 51 list the diseases Applicant intend to treat. 3) There is no working example of such a preventive procedure in man or animal in the specification. 4) The claims rejected are drawn to clinical preventive cancer medicine and are therefore physiological in nature. 5) The state of the art is that no general procedure is art-recognized for determining which patients generally will become prevented from getting a cancer before the fact. 6) The artisan using Applicants invention would be a Board Certified physician in the neurologic al disease with an MD degree and several years of experience. Despite intensive efforts, pharmaceutical science has been unable to find a way of getting a compound or its composition to be effective for the prevention of any neurologic al diseases generally. Under such circumstances, it is proper for the PTO to require evidence that such an unprecedented feat has actually been accomplished, In re Ferens, 163 USPQ 609. No such evidence has been presented in this case. The failure of skilled scientists to achieve a goal is substantial evidence that achieving such a goal is beyond the skill of practitioners in that art, Genentech vs. Novo Nordisk, 42 USPQ2nd 1001, 1006. This establishes that it is not reasonable to any agent to be able to prevent any c neurologic al disease generally. That is, the skill is so low that no composition effective generally against any cancers has ever been found let alone one that can prevent such conditions. 7) 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). 8) The claims broadly read on all patients, not just those undergoing therapy for the claimed diseases and on the multitude of composition containing various compounds.
The Examiner suggests deletion of the word “preventing” from the claim.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
5. Claim(s) 1-2. 5, 7-8, 10, 13, 16 and 19 are rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by Shanghai et al (EP 3778588 A1), which is equivalent to Shanghai et al (WO20191850460).
Shanghai et al discloses the following compound and its pharmaceutical composition :
PNG
media_image2.png
201
188
media_image2.png
Greyscale
(see page 43, compound# 28d).
This is identical with the claims .
.
6. Claim(s) 1-2. 5, 7-8, 10, 13, 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by PubChem ( Substance Record for SID 36391913, 25 May 2018).
PubChem discloses the following compound:
2-piperidin-3-yl-1,3-benzothiazole hydrochloride
PNG
media_image3.png
148
375
media_image3.png
Greyscale
.
This is identical with the claims .
7. Claim(s) 1-2. 5, 7-8, 10, 12 and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by Abraham et al (WO2011/085406).
Abraham et al discloses the following compounds and their pharmaceutical composition :
PNG
media_image4.png
112
182
media_image4.png
Greyscale
(see page 126, example 19, compound# 5C).;
PNG
media_image5.png
136
199
media_image5.png
Greyscale
. (see page 131, example 229, compound# 13).;
These are identical with the claims .
8. Claim(s) 1-2. 5, 7, and 9-11 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by PubChem ( Substance Record for SID 423892352, 2020-08-13).
PubChem discloses the following compound:
3-methyl-1-(oxetan-3-yl)piperidine
PNG
media_image6.png
244
316
media_image6.png
Greyscale
This is identical with the claims .
9. Claim(s) 1-2. 5, 7-8, 10, 12-14, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by PubChem ( Substance Record for CID 45073825, 2010-03-29).
PubChem discloses the following compound:
3-thiophen-2-ylpiperidine
PNG
media_image7.png
207
374
media_image7.png
Greyscale
This is identical with the claims .
10. Claim(s) 1-2. 5, 7-8, 10, 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated clearly by Showell et al ( J. Med. Chem., 1991, 34, 1066-1094).
Showell et al discloses the following compounds:
PNG
media_image8.png
110
129
media_image8.png
Greyscale
(see page 1086, compound#9)
PNG
media_image9.png
109
123
media_image9.png
Greyscale
(see page 1087, compound#4)
These are identical with the claims .
11. Claim(s) 1-2. 5, 7-8, 10-13 and 16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated clearly by Stolt et al (WO 2008/3736).
Stolt et al discloses some compounds and their pharmaceutical composition in the following:
PNG
media_image10.png
91
171
media_image10.png
Greyscale
PNG
media_image11.png
114
206
media_image11.png
Greyscale
(see page 21, Scheme 4, compounds# 25-26; page 53, table , comounds# 26A, 26B).
Furthermore, it teaches a pharmaceutical composition or formulation comprising a compound, is administered concurrently or sequentially or as a combined preparation with another therapeutic agent or agents, for treating one or more of the conditions listed (see page 9, lines 26-28) neuroendocrine, neurological and neuropsychiatric disorders, schizophrenia, memory and learning disabilities, attention deficit hyperactivity disorder, anxiety disorders, depressive disorders, neurodegenerative disorders (see page 8, lines 25-28)
These are identical with the claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
5. Claims 1-2, 5, 7-8, 10-13 and 16-19 are rejected under 35 U.S.C. 103 as being unpatentable over Stolt et al (WO 2008/3736).
Determination of the scope and content of the prior art
Stolt et al discloses some compounds and their pharmaceutical composition in the following:
PNG
media_image10.png
91
171
media_image10.png
Greyscale
PNG
media_image11.png
114
206
media_image11.png
Greyscale
(see page 21, Scheme 4, compounds# 25-26; page 53, table , comounds# 26A, 26B).
Furthermore, it teaches a pharmaceutical composition or formulation comprising a compound, is administered concurrently or sequentially or as a combined preparation with another therapeutic agent or agents, for treating one or more of the conditions listed (see page 9, lines 26-28) neuroendocrine, neurological and neuropsychiatric disorders, schizophrenia, memory and learning disabilities, attention deficit hyperactivity disorder, anxiety disorders, depressive disorders, neurodegenerative disorders (see page 8, lines 25-28)
The instant invention, however, differs from the prior art in that the claimed R2 being methyl is unspecified in the prior art.
Ascertainment of the difference between the prior art and the claims
The difference between the instant application and the applied Stolt et al art is that the Stolt et al does not expressly teach the claimed variable R2 being methyl .
Resolving the level of ordinary skill in the pertinent art.
Regarding the instant Claims 11, 17-18, with respect to the lack of disclosing the claimed R2 being methyl,, the prior art is silent about it.
However, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound.
So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to prepare the claimed compound as an alternative in the the Stolt et al method. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Stolt et al expressly discloses some compounds and their pharmaceutical composition in the following:
PNG
media_image10.png
91
171
media_image10.png
Greyscale
PNG
media_image11.png
114
206
media_image11.png
Greyscale
(see page 21, Scheme 4, compounds# 25-26).
Although Stolt et al does not teach that the claimed variable R2 is methyl, the distinction between the prior art and the claimed compound is hydrogen vs. methyl moiety; it is well-established that the substitution of methyl for hydrogen is a known compound is not a patentable modification absent unexpected or unobvious results. In re Wood, 582 F.2d 638, 199 U.S.P.Q. 137 (C.C.P.A. 1978); In re Hoke , 560 F. 2d 436, 195 U.S.P.Q. 148 (C.C.P.A. 1977). Furthermore, such a difference between the prior art and the claimed compound is a minor and can be expected to be prepared by the same method and to have generally the same or similar properties. This expectation is then deemed the motivation for preparing the methyl substituted compound.
So, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to prepare the claimed compound as an alternative in the the Stolt et al method. This is because the skilled artisan in the art would expect such a selection and manipulation to be successful and feasible as guidance shown in the prior art.
Conclusion
Claims 1-2, 5, 7-19 are rejected.
Claims 21-22 and 27-28 are withdrawn from consideration.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAYLOR V OH whose telephone number is (571)272-0689. The examiner can normally be reached 8:00-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant 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, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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.
/TAYLOR V OH/ Primary Examiner, Art Unit 1625
10/10/2026
Prosecution Insights