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 is a 371 of PCT/EP2021/079209, filed Oct. 21, 2021, and claims foreign priority to EP20203311.4 and EP21192154.9, filed Oct. 22, 2020 and Aug. 19, 2021, respectively, with the European Patent Office.
Claim Status
Claims 1-4, 8-21 and 23-24 are currently pending and subject to examination.
Claim Rejections – Withdrawn – Overcome by Amendment
The rejection of claims 4, 6, 8, 12, 14, 15, and 16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
The above rejection was overcome by amendment.
Claim Rejections - 35 USC § 103 – Previously Presented
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
The rejection of claim(s) 1-4, 8-14, 18-21 and 23-24 under 35 U.S.C. 103 as being unpatentable over Craig et al. (WO 2020/168011 A1, published August 20, 2020) (of record, IDS 04/21/2023, cite no. A5) in view of McCurdy & Cohen (Drug Design Org, Feb. 2007, p. 1-138) is maintained.
The rejection of claim(s) 1-4, 8-10, 15-21 and 23-24 under 35 U.S.C. 103 as being unpatentable over Craig et al. (WO 2019/046779 A1, published March 7, 2019) (of record, IDS 04/21/2023, cite no. A3) in view of McCurdy & Cohen (Drug Design Org, Feb. 2007, p. 1-138) is maintained.
Response to Arguments
The Applicant’s compounds differ from the compounds of Craig 2020 and Craig 2019 in that Craig’s compounds have a central tetrahydropyran ring or cyclohexane ring instead of a piperidine or 1,3-dioxane ring as the instantly claimed compounds. The Applicant argues that there is no reason or motivation to modify the compounds of Craig to arrive at the instantly claimed compounds (Remarks, p. 20-24). The Applicant argues that because McCurdy does not teach the modification in the context of the claimed invention, there would be no reason or motivation for one of ordinary skill in the art to modify Craig’s compounds to arrive at the compounds of the instant invention (id.). These arguments were fully considered but are not persuasive. A prima facie case of obviousness for chemical compounds is found when one of ordinary skill in the art would reasonably expect that compounds similar in structure would have similar properties (MPEP § 2144.09). The claimed compounds differ from the compounds of Craig by a single atom (C, N or O). One of ordinary skill in the art would have a reasonable expectation of success to exchange C, N or O for each other because McCurdy teaches that compounds with these bioisosteric replacements would have similar properties. McCurdy shows that it is common in the art to make these replacements to produce similar compounds with similar or improved properties, regardless of the exact structure of the compound. This is the entire concept of bioisosterism:
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McCurdy, p. 1.
Contrary to the Applicant’s assertion that the cited references do not teach to modify a central ring, McCurdy teaches that C, N and O atoms are divalent bioisosteres that are equivalent in the context of ring systems:
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McCurdy, p. 12;
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McCurdy, p. 14.
The Applicant argues that the claimed compounds have unexpected integrated stress response activity (Remarks, p. 20-21). These arguments were fully considered but are not persuasive. The claimed compounds exhibit the same activity as the compounds of Craig. For example, Craig (2020) teaches that example 5 has an IC50 of 13.4 nM in the AT4 integrated stress response pathway (Craig, Specification, p. 61, paragraph 264). This falls squarely within the activity range demonstrated for claimed example 2 (1-500 nM) which differs from Craig’s example 5 by a single atom. This supports the prima facie case of obviousness for the claimed compounds. One of ordinary skill in the art would reasonably expect that structurally related compounds would have similar properties (MPEP § 2144.09). The Applicant has not demonstrated that the claimed compounds possess unexpectedly advantageous or superior properties as compared to the prior art compounds.
Reiterated Rejection
Claim(s) 1-4, 8-14, 18-21 and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Craig et al. (WO 2020/168011 A1, published August 20, 2020) (of record, IDS 04/21/2023, cite no. A5) in view of McCurdy & Cohen (Drug Design Org, Feb. 2007, p. 1-138).
Claim 1 is directed towards a compound of formula (I):
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. For example,
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(Specification, p. 61).
Craig teaches the compound:
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(Craig, Specification, paragraph 165, Table 1, example 5). Craig teaches that this compound is “useful in treating and/or preventing diseases mediated, at least in part, by eukaryotic initiation factor 2B, such as neurodegenerative diseases (e.g., neurodegeneration in prion disease) and cancer.” (Id. paragraph 8)
Although Craig’s example 5 differs from instant example 2 by a single atom (oxane vs. piperidine), one of ordinary skill in the art would have a reasonable expectation of success to substitute O for NH in the six membered ring because this is a bioisosteric replacement commonly known to produce compounds with similar properties.
For example, McCurdy teaches that NH is equivalent to O:
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McCurdy, p. 12.
Although Craig’s example 5 has a different stereochemistry from example 2, one of ordinary skill in the art would have a reasonable expectation of success that the stereoisomers would have similar properties because stereoisomers are prima facie obvious and are presumed to have similar properties. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
For example, Craig teaches both (3S, 6R) isomers and (3R, 6S) isomers and that they have similar properties:
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(Craig, Specification, paragraph 239).
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(Craig, Specification, paragraph 236).
Therefore, claim 12 was prima facie obvious at the time of filing.
Claims 2, 4-14, 18-19, and 20 read on example 2 and are therefore prima facie obvious for the reasons given in the rejection of claim 1.
Claim 3 is directed towards the compound of claim 1, wherein the compound is a compound of formula (I-2):
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While a compound of formula (I-2) differs from Craig’s example 5 by a single atom (X1 and X2 are both O in the compound of formula (I-2), while only X is O in Craig’s example 5), one of ordinary skill in the art would have a reasonable expectation of success to substitute CH2 for O as X2 because this is a bioisosteric replacement commonly known to produce compounds with similar properties. For example, see McCurdy, p. 12 cited in the rejection of claim 1 above.
Therefore, claim 3 was prima facie obvious at the time of filing.
Claim 21 is directed towards a pharmaceutical composition comprising:
At least one compound of claim 1 and
At least one pharmaceutically acceptable carrier, optionally in combination with one or more other bioactive compounds or pharmaceutical compositions.
One of ordinary skill in the art would have a reasonable expectation of success to formulate such a pharmaceutical composition because similar compositions are commonly known in the art. For example, Craig teaches a pharmaceutical composition comprising a compound comparable to claim 1 in combination with “one or more pharmaceutically acceptable vehicles selected from carriers, adjuvants, and excipients” (Craig, Specification, paragraph 195).
Therefore, claim 21 was prima facie obvious at the time of filing.
Claim 23 is directed towards a method of treating or preventing one or more diseases or disorders associated with the integrated stress response comprising administering to the subject in need a compound of claim 1.
One of ordinary skill in the art would have a reasonable expectation of success to treat or prevent one or more diseases or disorders associated with the integrated stress response with the compound of claim 1 because similar compounds are known for the treatment of conditions associated with the integrated stress response.
For example, Craig teaches compounds such as example 5 for treating diseases mediated by eukaryotic initiation factor 2B (Craig, specification, paragraph 2) which is associated with the integrated stress response: “The interaction between eukaryotic initiation factor 2B and eukaryotic initiation factor 2 plays an important role in the integrated stress response (ISR) pathway.” (Id., paragraph 6). Craig teaches that the compound inhibit the integrated stress response pathway:
In another embodiment, provided is a method for inhibiting the integrated stress response pathway, the method comprising administering an effective amount of the pharmaceutical composition comprising a compound.
Id., paragraph 18.
Craig evaluated the compounds in an integrated stress response assay (Id., paragraph 263-264).
Therefore, claim 23 was prima facie obvious at the time of filing.
Claim 24 is directed towards the method of claim 23, wherein the disease or disorders are selected from the group consisting of leukodystrophies, intellectual disability syndrome, neurodegenerative diseases and disorders, neoplastic diseases, infectious diseases, inflammatory diseases, musculoskeletal diseases, metabolic diseases, ocular diseases, organ fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, myocardial infarction, cardiovascular disease, arrhythmias, atherosclerosis, spinal cord injury, ischemic stroke, and neuropathic pain.
One of ordinary skill in the art would have a reasonable expectation to treat such conditions with the compound of claim 1 because similar compounds are known for the treatment of these conditions.
For example, Craig teaches the treatment of:
cancer, pre- cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation.
Craig, Specification, paragraph 176.
Therefore, claim 24 was prima facie obvious at the time of filing.
Claim(s) 1-4, 8-10, 15-21 and 23-24 is/are rejected under 35 U.S.C. 103 as being unpatentable over Craig et al. (WO 2019/046779 A1, published March 7, 2019) (of record, IDS 04/21/2023, cite no. A3) in view of McCurdy & Cohen (Drug Design Org, Feb. 2007, p. 1-138).
Claim 1 is directed towards a compound of formula (I):
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. For example,
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(Specification, p. 86, example 52).
Craig teaches the compound:
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(Craig, Specification, paragraph 234, Table 1, example 56). Craig teaches that is “useful in treating and/or preventing diseases mediated, at least in part, by eukaryotic initiation factor 2B, such as neurodegenerative diseases (e.g., neurodegeneration in prion disease) and cancer.” (Id. paragraph 8)
Although Craig’s example 56 differs from instant example 52 in two rings, oxane vs. piperidine and the point of attachment to the quinoline, one of ordinary skill in the art would have a reasonable expectation of success to substitute O for NH in the six membered ring and change the point of attachment to the quinoline because these are a bioisosteric replacements commonly known to produce compounds with similar properties.
For example, McCurdy teaches that NH is equivalent to O and CH to N:
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McCurdy, p. 12;
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McCurdy, p. 13;
Therefore, claim 1 was prima facie obvious at the time of filing.
Claims 2, 4-10, 15-18 and 20 read on the compound example 52. Therefore, claims 2, 4-10, 15-18 and 20 were prima facie obvious at the time of filing.
Claim 3 is directed towards the compound of claim 1, wherein the compound is a compound of formula (I-2):
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While a compound of formula (I-2) differs from Craig’s example 56 by a single atom (X1 and X2 are both O in the compound of formula (I-2), while only X is O in Craig’s example 5), one of ordinary skill in the art would have a reasonable expectation of success to substitute CH2 for O as X2 because this is a bioisosteric replacement commonly known to produce compounds with similar properties. For example, see McCurdy, p. 12 cited in the rejection of claim 1 above.
Therefore, claim 3 was prima facie obvious at the time of filing.
Claim 19 is directed towards a compound of formula (IIb):
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.
One of ordinary skill in the art would have a reasonable expectation of success to generate a compound of formula (IIb) with similar properties to the compound of Craig because Craig teaches compounds with this stereochemistry. For example,
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(Craig, Specification, paragraph 234, Table 1, compound 75). For the reasons given in the rejection of claims 1 and 3, one of ordinary skill in the art would have a reasonable expectation of success to modify X1 and X2 to be as instantly claimed.
Therefore, claim 19 was prima facie obvious at the time of filing.
Claim 21 is directed towards a pharmaceutical composition comprising:
At least one compound of claim 1 and
At least one pharmaceutically acceptable carrier, optionally in combination with one or more other bioactive compounds or pharmaceutical compositions.
One of ordinary skill in the art would have a reasonable expectation of success to formulate such a pharmaceutical composition because similar compositions are commonly known in the art. For example, Craig teaches a pharmaceutical composition comprising a compound comparable to claim 1 in combination with “one or more pharmaceutically acceptable vehicles selected from carriers, adjuvants, and excipients” (Craig, Specification, paragraph 262).
Therefore, claim 21 was prima facie obvious at the time of filing.
Claim 23 is directed towards a method of treating or preventing one or more diseases or disorders associated with the integrated stress response comprising administering to the subject in need a compound of claim 1.
One of ordinary skill in the art would have a reasonable expectation of success to treat or prevent one or more diseases or disorders associated with the integrated stress response with the compound of claim 1 because similar compounds are known for the treatment of conditions associated with the integrated stress response.
For example, Craig teaches compounds such as example 56 for treating diseases mediated by eukaryotic initiation factor 2B (Craig, specification, paragraph 2) which is associated with the integrated stress response: “The interaction between eukaryotic initiation factor 2B and eukaryotic initiation factor 2 plays an important role in the integrated stress response (ISR) pathway.” (Id., paragraph 6). Craig teaches that the compound inhibit the integrated stress response pathway:
In another embodiment, provided is a method for inhibiting the integrated stress response pathway, the method comprising administering an effective amount of the pharmaceutical composition comprising a compound.
Id., paragraph 18.
Craig evaluated the compounds in an integrated stress response assay (Id., paragraph 468-469).
Therefore, claim 23 was prima facie obvious at the time of filing.
Claim 24 is directed towards the method of claim 23, wherein the disease or disorders are selected from the group consisting of leukodystrophies, intellectual disability syndrome, neurodegenerative diseases and disorders, neoplastic diseases, infectious diseases, inflammatory diseases, musculoskeletal diseases, metabolic diseases, ocular diseases, organ fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, myocardial infarction, cardiovascular disease, arrhythmias, atherosclerosis, spinal cord injury, ischemic stroke, and neuropathic pain.
One of ordinary skill in the art would have a reasonable expectation to treat such conditions with the compound of claim 1 because similar compounds are known for the treatment of these conditions.
For example, Craig teaches the treatment of:
cancer, pre- cancerous syndromes and diseases/injuries associated with activated unfolded protein response pathways, such as Alzheimer's disease, neuropathic pain, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, Parkinson's disease, diabetes, metabolic syndrome, metabolic disorders, Huntington's disease, Creutzfeldt-Jakob Disease, fatal familial insomnia, Gerstmann-Straussler-Scheinker syndrome, and related prion diseases, amyotrophic lateral sclerosis, progressive supranuclear palsy, myocardial infarction, cardiovascular disease, inflammation, organ fibrosis, chronic and acute diseases of the liver, fatty liver disease, liver steatosis, liver fibrosis, chronic and acute diseases of the lung, lung fibrosis, chronic and acute diseases of the kidney, kidney fibrosis, chronic traumatic encephalopathy (CTE), neurodegeneration, dementias, frontotemporal dementias, tauopathies, Pick's disease, Neimann-Pick's disease, amyloidosis, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation.
Craig, Specification, paragraph 243.
Therefore, claim 24 was prima facie obvious at the time of filing.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Conclusion
No claim is found to be allowable.
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 extension fee 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 HEATHER DAHLIN whose telephone number is (571)270-0436. The examiner can normally be reached 9-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on (571) 272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HEATHER DAHLIN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629