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 .
Election/Restrictions
Applicant’s election without traverse of compound 35 recited in claim 81 in the reply filed on January 7, 2026 is acknowledged.
The elected species has the following structural formula
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This compound corresponds to the compound of Formula I according to claim 1 wherein:
X1 and X2 both represent “C(RA)2” RA represents H and ---- represents a single bond;
R1 represents methyl;
R2 represents phenyl;
R3 represents -N-morpholine.
The elected compound was found in the search as obvious over Shinn et al. (see below). The search and examination was expanded to embrace compounds of Formula I according to claim 1 wherein X1 and X2 both represent C(RA)2 or CO, the 5H-Pyrrolo[2,3-d]pyrimidine core along with the full scope of the remaining variables.
Subject matter not falling under this group is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse.
Improper Markush Rejection
Claims 67-87 are rejected under a judicially created doctrine as being drawn to an improper Markush group, that is, the claims lack unity of invention. The variables X1, X2 and ---- are defined in such a way that they keep changing the core of the compound that determines the classification. By changing these values, several patentably distinct and independent compounds are claimed. In order to have unity of invention the compounds must have “a community of chemical or physical characteristics” which justify their inclusion in a common group, and that such inclusion is not repugnant to principles of scientific classification” In re JONES (CCPA) 74 USPQ 149 (see footnote 2). Formula (I) does not have a significant structural feature that is shared by all of its alternatives which is inventive. The structure has only a fused pyrimidine as common. This feature is not inventive (see prior art rejections below). Compounds embraced by Formula (I) are so diverse in nature that a prior art anticipating a claim with respect to one member under 35 USC 102 would not render obvious the same claim under 35 USC 103. This is evidentiary of patentably distinct and independent inventions.
Limiting the claims to the group indicated as having been searched would overcome this rejection.
Claim Rejections - 35 USC § 112
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 67 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, 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 applicant), regards as the invention.
i) The groups “C1-9 heterocyclyl” and “C1-9 heteroaryl” term “heteroaryl” are indefinite because these groups cannot be made up of solely 1-9 carbon atoms and require the presence of a heteroatom. It is not known how many and which heteroatoms are present, what size ring is intended and how many rings are present. In addition, in heterocyclyl, it is unclear what degree of saturation is required. Clarity is lacking at this point of novelty. A clarification is required.
ii) The term “substituted” without saying which substituents are intended is indefinite. One skilled in the art cannot say which substituents are permitted and which ones are not.
iii) In the definition of R1 as “an optionally substituted oxazolyl group, or a pyrid-2-on-1-yl group,” regarding pyrid-2-on-1-yl, is this a substituted group? Also, is this from pyridone (2- or 3-oxo pyridinyl)? See rejection below. A clarification is required.
iv) The composition in claims 68, 75 and 82 and should be limited to a “pharmaceutical composition” because the intended use is as a pharmaceutical and as indicated by having the pharmaceutically acceptable carrier.
Claim 81 has over 100 independent species. This number of compounds cannot be considered a reasonable number according to rule 1.141(a). In re Fressola, 22 USPQ 2nd 1828, indicates that the Examiner may reject for Applicants failure to follow a Rule.
§ 1.141 Different inventions in one national application.
(a) Two or more independent and distinct inventions may not be claimed in one
national application, except that more than one species of an invention, not to
exceed a reasonable number, may be specifically claimed in different claims in
one national application, provided the application also includes an allowable claim
generic to all the claimed species and all the claims to species in excess of one are
written in dependent form (§1.75) or otherwise include all the limitations of the
generic claim.
Applicants need to rewrite the claim as a dependent claim or as a series of independent claims wherein each claim has no more than a reasonable number of species per claim.
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 69-73, 76-80 and 83-87 are 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 claims 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 use the invention.
The claims are drawn to a method of treating a neurological disorder;
The method, wherein the neurological disorder is FTLD-TDP, chronic traumatic encephalopathy, ALS, Alzheimer's disease, LATE, or frontotemporal lobar degeneration;
A method of inhibiting toxicity in a cell related to a protein;
The method wherein the toxicity is TDP-43-related toxicity or C9orf72-related toxicity; and;
A method of inhibiting PIKfyve in a cell expressing PIKfyve protein.
Regarding claims 71-73, 78-80 and 85-87, these claims would read on inhibiting toxicity in a cell related to a protein, inhibiting toxicity is TDP-43-related toxicity or C9orf72-related toxicity or inhibiting PIKfyve in a cell expressing PIKfyve protein in vitro, inhibitions in mammals with below normal activity, inhibition in mammals with normal activity, or in asymptomatic mammals with up-regulated activity. The specification fails to teach any benefit to be gained from such actions. Is extensive experimentation required on the part of a potential infringer to determine if his use of Applicants' inhibitor falls within the limitations of applicants' claim? In re Kirk and Petrow, 153 USPQ 48 (CCPA 1967). As the Supreme Court said in Brenner v. Manson, 148 USPQ at 696: “a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.” As U.S. Court of Customs and Patent Appeals stated In re Diedrich 138 USPQ at 130, quoting with approval from the decision of the board: “We do not believe that it was the intention of the statutes to require the Patent Office, the courts, or the public to play the sort of guessing game that might be involved if an applicant could satisfy the requirements of the statutes by indicating the usefulness of a claimed compound in terms of possible use so general as to be meaningless and then, after his research or that of his competitors has definitely ascertained an actual use for the compound, adducing evidence intended to show that a particular specific use would have been obvious to men skilled in the particular art to which this use relates.”
Regarding claims 69, 70, 76, 77, 83 and 84 there are no known compounds of which have been demonstrated to treat neurological disorders generally. There is no such an agent because neurological disorders are extremely varied in origin and nature of effect. The origins, symptoms and the nature of many neurological disorders such as Huntington's disease, Pick's disease, Frontotemporal dementia, Cerebro-Oculo-Facio-Skeletal (COFS) syndrome (cranofacial and skeletal abnormalities), Motor neuron disease (muscle weakness), Corticobasal ganglionic degeneration, Creutzfeldt-Jacob disease (fatal disease), Dementia with Lewy bodies, and Progressive supranuclear palsy Dementia are different one from the other. Many are untreatable to this day.
Many neurological disorders vary in how they affect the body and its functions. Diseases such as Cerebral palsy, and Parkinson's disease affect the movement of the patient. Diseases such as Alzheimer's disease affect the memory of the patient. Neurological disorders such as Depression, Meningitis (viral, bacteria, or fungi infection), Encephalitis (viral infection), Rett syndrome, Tinnitus, Narcolepsy, Shy-Drager syndrome, Charcot-Marie-Tooth disease, Tarsal tunnel syndrome, Psychosis, Memory loss, Mental retardation, Autism, Migraine, Tension headache, Multiple sclerosis, etc. are different one from the other. The symptoms and nature of these diseases are also different one from the other. Some are hereditary (Charcot-Marie-Tooth disease). Since the origin and nature of neurological disorders vary extremely one from the other, it is impossible to treat them in general.
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).
Also, see In re Surrey 151 USPQ 724, regarding sufficiency of a disclosure for a Markush group, and MPEP 2164.03 for enablement requirements in cases directed to structure-sensitive arts such as the instant pharmaceutical arts. Note in Surrey, in which testing done on a group of homogeneous compounds having the same core was deemed NOT sufficient to support claims to various hetero groups of a much narrower range than is being claimed herein and located at only one position in the formula.
There are no doses present to direct one to treat any and all of the disorders embraced by the claims. The claims are drawn to disorders that are not related and whose treatment is unknown.
The origin and the nature of many neurodegenerative disorders, such as, Huntington’s disease, Pick’s disease, Frontotemporal dementia, Cerebro-Oculo-Facio-Skeletal (COFS) syndrome (cranofacial and skeletal abnormalities), Motor neuron disease (muscle weakness), Corticobasal ganglionic degeneration, Creutzfeldt-Jacob disease (fatal disease), Dementia with Lewy bodies, and Progressive supranuclear palsy Dementia are different one from the other. Many neurodegenerative disorders are untreatable to this day.
The symptoms and nature of these diseases are also different one from the other. It can be shown that many of these diseases have different origin and nature of effect. Some are hereditary (Charcot-Marie-Tooth disease). Many vary in how they affect the body and its functions. Diseases such as Cerebral palsy, and Parkinson’s disease affect the movement of the patient. Diseases such as Alzheimer’s disease affect the memory of the patient.
The scope of uses embraced by these claims are not remotely enabled based solely on instant compounds ability to inhibit PIKfyve. Applicants need to limit the claims to those disorders that are known to be treated.
Case law is clear on this point. In an unpredictable art, models may be used for enablement only if there is a well-established correlation between the assay and clinical efficacy.
Applicants have not demonstrated nor have they alleged there is any correlation between the in vitro assays they disclose and clinical efficacy against any disease.
Copious amount of art was found.
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.
Claims 67, 68, 74 and 75 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Choi et al. (Bioorganic & Medicinal Chemistry Letters (2006), 16(8), 2173-2176). The claim reads on the compound depicted below. See Abstract.
RN 885702-55-6 CAPLUS
CN 7H-Pyrrolo[2,3-d]pyrimidine, 2-(4-morpholinyl)-7-(2-pyridinyl)-
(CA INDEX NAME)
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Claims 67, 68, 74 and 75 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shimma et al. (US 8022205). The claims reads on numerous compounds of the reference Examples and intermediates, such as, the structure in column 425, Step C.
RN 1007206-76-9 CAPLUS
CN 2(1H)-Pyridinone, 5-[6,7-dihydro-2-(4-morpholinyl)-7-(3-
pyridinyl)-5H-pyrrolo[2,3-d]pyrimidin-4-yl]- (CA INDEX NAME)
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373
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RN 1007206-77-0 CAPLUS
CN 2(1H)-Pyridinone, 5-[6,7-dihydro-2-(4-morpholinyl)-7-(4-
pyridinyl)-5H-pyrrolo[2,3-d]pyrimidin-4-yl]- (CA INDEX NAME)
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304
376
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RN 1007206-78-1 CAPLUS
CN 2(1H)-Pyridinone, 3-[6,7-dihydro-2-(4-morpholinyl)-7-(3-
pyridinyl)-5H-pyrrolo[2,3-d]pyrimidin-4-yl]- (CA INDEX NAME)
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284
349
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RN 1007206-24-7 CAPLUS
CN 5H-Pyrrolo[2,3-d]pyrimidine, 4-chloro-6,7-dihydro-2-(4-
morpholinyl)-7-(3-pyridinyl)- (CA INDEX NAME)
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241
298
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RN 1007206-25-8 CAPLUS
CN 5H-Pyrrolo[2,3-d]pyrimidine, 4-chloro-6,7-dihydro-2-(4-
morpholinyl)-7-(4-pyridinyl)- (CA INDEX NAME)
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294
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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.
Claims 67, 68, 74, 75, 81 and 82 is/are rejected under 35 U.S.C. 103 as being unpatentable over Shimma et al. (US 8022205). The reference teaches a generic group of compounds which embraces applicants’ claimed compounds (See cols 4-8, compounds of formula (I’) and definitions of the variables). The claims differ from the reference by reciting specific species and a more limited genus than the reference. However, it would have been obvious to one having ordinary skill in the art at the time of the invention to select any of the species of the genus taught by the reference, including those instantly claimed, because the skilled chemist would have the reasonable expectation that any of the species of the genus would have similar properties and, thus, the same use as taught for the genus as a whole. One of ordinary skill in the art would have been motivated to select the claimed compounds from the genus in the reference since such compounds would have been suggested by the reference as a whole. It has been held that a prior art disclosed genus of useful compounds is sufficient to render prima facie obvious a species falling within a genus. In re Susi, 440 F.2d 442, 169 USPQ 423, 425 (CCPA 1971), followed by the Federal Circuit in Merck & Co. v. Biocraft Laboratories, 847 F.2d 804, 10 USPQ 2d 1843, 1846 (Fed. Cir. 1989).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRUCK KIFLE whose telephone number is (571)272-0668. The examiner can normally be reached 8 AM - 6 PM, M-F.
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, Jeffrey H. Murray can be reached at 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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March 21, 2026
/BRUCK KIFLE/Primary Examiner, Art Unit 1624