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 .
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 .
Claims 29-54 are pending in the instant application. Claim 54 is rejected. Claims 29-53 are allowed.
Information Disclosure Statement
The information disclosure statement filed on November 5, 2025 has been considered and a signed copy of 1449 is enclosed herewith.
Response to Amendment and Arguments/Remarks
The amendment and arguments/remarks filed on October 15, 2025 have been fully considered and entered into the application. With regards to the 35 U.S.C. 112(a) rejection, Applicant argues “claims 54 has been amended in a manner believed to fully address the Examiner’s comments.” This argument in view of the amendment is not found to be persuasive. Even though the claim now lists specific examples of each broad class of diseases or disorders, the examiner is still of the belief that there is not one class of compounds, let alone one compound, which can treat all of the diseases or disorders listed in the claims. For example, with regards to the neurodegenerative diseases and disorders listed in the claim, this covers a large array of largely unrelated diseases or disorders that have different modes of action and different origins. Many diverse diseases or disorders are listed, such as Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, frontotemporal dementia, Huntington’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, spinocerebellar ataxias, Pick’s disease, prion diseases, etc. Current pharmacological therapies offer symptomatic benefits with very little impact, if any, in modifying the course of these diseases. Anticholinesterase drugs are the most frequently used to treat Alzheimer’s disease and levodopa is the most effective pharmacological treatment for Parkinson’s disease. There is no approved pharmacological treatment for most other forms of neurodegenerative diseases except for amyotrophic lateral sclerosis, Huntington disease and some forms of cerebellar ataxias. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48). Many of neurodegeneration diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemical, and viruses. Sometimes the cause is unknown. See https://medlineplus.gov/degenerativenervediseases.html. In other words, these diseases or disorders exhibit a very broad range of effects and origins. Therefore, unlike in some areas of medicine, there is no representative, or "typical" neurodegenerative disorder. Some affect the mind, some affect movement, some affect both, and some affect neither. As a further example, Alzheimer's disease and Parkinson’s disease are the most common neurodegenerative disorder. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48). However, the etiology of Alzheimer’s disease involves both tau protein and 13-amyloid. Such a statement is not true for any other important neurodegenerative disorder, and indeed the vast majority of neurodegenerative disorders involve neither one of those. Therefore, as disclosed in the previous Office Action, the specification fails to provide sufficient support of the broad use of the compounds of the instant claims for the treatment of the various claimed diseases or disorders, as a result necessitating one of skill to perform an exhaustive search for which diseases or disorders can be treated by what compounds of the instant claims in order to practice the claimed invention. Only several of the claimed diseases or disorders are discussed here to make the point of an insufficient disclosure, it does not mean that the other diseases or disorders meet the enablement requirements. Working examples which support the treatment of each of the claimed diseases or disorders or non-patent literature citations that discuss the relationships between modulation of the integrated stress response pathway and each of the claimed diseases or disorders are lacking from the specification. As a result, the rejection is maintained (but altered slightly) and described below.
Maintained 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.
Claim 54 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.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include: nature of the invention, breadth of the claims, guidance of the
specification, the existence of working examples, state of the art, predictability of the art
and the amount of experimentation necessary. All of the Wands factors have been
considered with regard to the instant claims, with the most relevant factors discussed
below.
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is that the pharmacological art 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 or
disorder by what mechanism). 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.
The instantly claimed invention is highly unpredictable as discussed below: 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 statue. In the instant case, the claimed
invention is highly unpredictable since one skilled in the art would recognize that in
regards to therapeutic effects, whether or not the disease or disorder is affected by the
modulation of the integrated stress response pathway or by the administration of a therapeutically effective amount of a compound of formula (I) would make a difference.
With regards to the treatment of the plethora of diseases or disorders listed in the claim, this method could include many unrelated diseases or conditions (i.e., many of which have a different cause and, therefore, require a different treatment). There is not one class of compounds, let alone one compound, which can treat all of the diseases or disorders listed in the claims.
For example, the specific neurodegenerative diseases and disorders listed covers a large array of largely unrelated disorders that have different modes of action and different origins. Many diverse diseases or disorders are listed, such as Alzheimer’s disease, Parkinson’s disease, Lewy body dementia, frontotemporal dementia, Huntington’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, spinocerebellar ataxias, Pick’s disease, prion diseases, etc. Current pharmacological therapies offer symptomatic benefits with very little impact, if any, in modifying the course of these diseases. Anticholinesterase drugs are the most frequently used to treat Alzheimer’s disease and levodopa is the most effective pharmacological treatment for Parkinson’s disease. There is no approved pharmacological treatment for most other forms of neurodegenerative diseases except for amyotrophic lateral sclerosis, Huntington disease and some forms of cerebellar ataxias. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48).
Many of neurodegeneration diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemical, and viruses. Sometimes the cause is unknown. See https://medlineplus.gov/degenerativenervediseases.html. In other words, these diseases exhibit a very broad range of effects and origins. Therefore, unlike in some areas of medicine, there is no representative, or "typical" neurodegenerative disorder. Some affect the mind, some affect movement, some affect both, and some affect neither.
Alzheimer's disease and Parkinson’s disease are the most common neurodegenerative disorder. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48). However, the etiology of Alzheimer’s disease involves both tau protein and 13-amyloid. Such a statement is not true for any other important neurodegenerative disorder, and indeed the vast majority of neurodegenerative disorders involve neither one of those.
Hence, in the absence of a showing of correlation between all the diseases or disorders claimed as capable of treatment through the modulation of the integrated stress response pathway or through the administration of a therapeutically effective amount of a compound of formula (I), one of skill in the art is unable to fully predict possible results from the administration of the compounds of the claims due to the unpredictability.
The amount of direction or guidance present and the presence or absence of
working examples
A disclosure should contain representative examples which provide reasonable
assurance to one skilled in the art that the compounds which fall within the scope of a
claim will possess the alleged activity. The only direction or guidance present in the instant specification is non-patent literation citations which disclose the involvement of the integrated stress response pathway in some of the diseases or disorders listed in the claims (see pages 1-3 of the specification), the listing of diseases or disorders Applicant considers as treatable by the administration of a compound of formula (I), and an in vitro assay measuring the prevention of Tunicamycin induced ISR (see pages 62-63). However, the specification does not contain any evidentiary support that these compounds would be able to treat the plethora of diseases or disorders listed. Furthermore, there are no working examples to support the treatment of the instantly claimed diseases or disorders.
Applicant has not provided any competent evidence or disclosed tests that are
highly predictive for the pharmaceutical use of the instant compounds and
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).
The level of 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 or disorders would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the
compounds of the instant claims for the treatment of the various claimed
diseases or disorders, as a result necessitating one of skill to perform an exhaustive search for which diseases or disorders can be treated by what compounds of the instant claims in order to practice the claimed invention. Only several of the claimed diseases or disorders are discussed here to make the point of an insufficient disclosure, it does not mean that the other diseases or disorders meet the enablement requirements.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in
the art would need to determine what specific diseases or disorders are benefited by the
administration of the compounds of the instant claims and would furthermore have to
determine which of the claimed compounds would provide treatment of which diseases or disorders.
Factors such as "sufficient working examples", "the level of skill in the art" and
"predictability", etc. have been demonstrated to be sufficiently lacking in the instantly
claimed methods. In view of the chemical nature of the invention and the lack of working
examples regarding the activity of the claimed compounds, one having ordinary skill in
the art would have to undergo an undue amount of experimentation to use the invention
commensurate in scope with the claims.
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 "patent 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, a person of skill in the art would have to
engage in undue experimentation to test which specific diseases or disorders can be treated by the compounds encompassed in the instant claims, with no assurance of success.
This rejection can be overcome by disclosing working examples which support the treatment of each of the claimed diseases or disorders or non-patent literature citations that discuss the relationships between modulation of the integrated stress response pathway and each of the claimed diseases or disorders listed in the claim.
Allowable Subject Matter
Claims 29-53 are allowed. No prior art was found.
Conclusion
THIS ACTION IS MADE FINAL. 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 KRISTIN ANN VAJDA whose telephone number is (571)270-5232. The examiner can normally be reached Mon-Fri 6:00-4:00.
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/KRISTIN A VAJDA/Primary Examiner, Art Unit 1622