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
This application was filed 02/09/2023 and is a 371 of PCT/US2021/045446 (08/10/2021) which has a PRO 63/064262 (08/11/2020).
Election/Restrictions
Applicant’s election of group II in the reply filed on 12/22/2025 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)).
Applicant has deleted all claims and inserted new claims 90-109 directed solely to elected group II and method of treatment claim directed to group II with the restriction election dated 12/22/2025.
Claim Rejections - 35 USC § 112
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 94 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. Claim 94 (which depends from claim 93) has the limitation of R6 is F or CF3. Claim 93 has R6 as halo; this does not include CF3. 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.
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.
Claim 109 is 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(s), at the time the application was filed, had possession of the claimed invention. The instant specification does not adequately describe the nexus between the regulation of protein synthesis, degradation, folding, trafficking and aggregation within a cell (proteostasis) and a useful treatment of a disease/condition. Applicant teaches that proteostasis is maintained by a wide array of cellular machinery that work to ensure that proteins are present in the proper location, amounts and form to perform their respective functions. And when one or more of the pathways involved with proteostasis becomes dysregulated, there are disastrous effects on the cell and neighboring cells. Neurodegenerative diseases can accumulate specific aggregation prone proteins which lead to toxic signaling and disruption of proteostasis caused by their uncontrolled aggregation and oligomerization. Neurodegenerative diseases can begin as a result of one of several disruptions (e.g. mutations, changes in expression, oxidative stress, aging, proteasome impairment, etc.) to their normal regulation. Applicant further teaches that α-syn has a role in the disease but may not be the sole cause of the disease. It is not seen where the instant specification adequately describes the nexus between the modulation of α-syn and a useful treatment of a single disease or condition.
Claim 109 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue”. These factors include 1) the breadth of the claims, 2) the nature of the invention, 3) the state of the prior art, 4) the level of one of ordinary skill, 5) the level of predictability in the art, 6) the amount of direction provided by the inventor, 7) the existence of working examples, and 8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The nature of the invention: The nature of the invention is the method of (i) treating a neurodegenerative disease; (ii) reducing, substantially eliminating or eliminating dysregulation of proteostasis; or (iii) reducing, substantially eliminating or eliminating the accumulation of intrinsically disordered proteins.
The state of the prior art: The state of the prior art is that it involves screening in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific disease). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic regimen on its face. Currently there is no known treatment for all neurodegenerative diseases with one activity/drug. Further, the nexus between proteostasis or the accumulation of intrinsically disordered proteins and a treatment of a disease is not currently accepted by the ordinary artisan. There is a link but the ability to treat a disease by modulating this link is not known or accepted.
The predictability in the art: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F. 2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to the therapeutic effects of all diseases, whether or not the modulation of bradykinin receptors would make a difference in the disease. Hence, in the absence of a showing of a nexus between all known neurodegenerative diseases and the modulation of proteostasis or the reduction, substantial or full elimination of the accumulation of intrinsically disordered proteins or dysregulation of proteostasis and how this is linked to the treatment of a condition, there is no known predictability in the art.
The presence or absence of working examples: There are no working examples in the instant specification of any compound treating a neurodegenerative disease. There are no working examples of the compounds of formula (II) and the dysregulation of proteostasis or disordered proteins. There appear to be no specific compounds of formula (II) made in the instant specification. Pages 52-54 of the specification teach of testing, however, the only compound that appears to have been tested for any activity is fluspirile which is not of formula (II).
The amount of direction or guidance present: The guidance present in the specification is that of the compounds of the invention have utility and can be used to treat neurodegenerative diseases or work on the dysregulation of proteostasis or the accumulation of intrinsically disordered proteins. However, the guidance has not provided a nexus between the activity of the compounds and the activity claimed in claim 109. Further, the nexus between the claimed activity in vitro and the in vivo relevance of the activity has not been taught/given. The specification does not seem to enable a correlation between the activity of the compounds and the treatment of diseases.
The breadth of the claims: The claims are drawn to the treatment of all neurodegenerative diseases mediated by the activity of the compounds of formula (II).
The quantity of experimentation needed: The quantity of experimentation needed is undue. One skilled in the art would need to determine what the nexus is between the alleged activity of the instant compounds and the real world activity of the compounds. Then, if the claimed activity of the compounds would lead to the benefit of the claimed activity. Further, then to determine if all neurodegenerative diseases could be treated by the claimed activity and that this would provide treatment of the disease.
The level of the skill in the art: The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the compounds of the claims for the treatment of a disease. As a result necessitating one of ordinary skill to perform an exhaustive search for which diseases can be treated by which compound of the claims in order to practice the claimed invention.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, one of ordinary skill in the art would have to engage in undue experimentation to test which diseases can be treated by the compounds of the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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.
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.
Claims 90-92, 95-98, 100, 104, 108 and 109 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pajouhesh. Pajouhesh teaches compounds for pharmaceutical use in Fig 1 page 1378 where X1 is alkyl, X2 is CR5 and R5 is H (resulting in X2 being CH), X3 being NR8 and R8 is alkyl (arylalkyl), R6 is H as calcium channel inhibitors having anti-allodynic activity.
Claims 90-102, 104, 108 and 109 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zamponi. Zamponi teaches compounds in Fig 3, scheme 1 and scheme 2 as well as tables 4, 5 and 6 that anticipate the instant claims. Fig 3 and scheme 1 and 2 compounds anticipate claims 90-98, 100, 104, 108 and 109. Compounds NP118809 page 6469 as well as compounds in fig 3 anticipate claims 99, 101 and 102. Compounds in table 5 anticipate claims 101 and 102. Table 6 has R6 as halogen and H. These compounds are potent N-type calcium channel blockers.
Claims 90-102, 104, 108 and 109 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Obinska, Ogiyama and Gleeson. Obinska teaches compounds of series 2 as being anticonvulsants. Obiyama teaches compound 3 as being orally active N-type calcium channel blockers. Gleeson teaches Z160 in figure 1 as a calcium channel inhibitor. These anticipate the instant claims.
Claims 90-92, 95-96, 104-105, 108 and 109 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zakusilo teaches 3c and 2m in scheme 2 having X as CR8 and R8 as H anticipating the instant claims.
Claim Objections
Claims 103 and 106-107 are objected to because of the following informalities: These claims are free of prior art but depend from a rejected base claim. These claims would be allowable if rewritten in independent form with all intervening limitations. Appropriate correction is required.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D MARGARET M SEAMAN whose telephone number is (571)272-0694. The examiner can normally be reached M-F 8am-4pm Eastern.
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/D MARGARET M SEAMAN/ Primary Examiner, Art Unit 1625