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 .
Receipt is acknowledged of Applicant’s Restriction Requirement Response and Amendment filed on 05/26/2026; and IDS filed on 06/18/2026, 05/26/2026, and 05/18/2023.
Claims 4 and 6 have been amend.
Claims 4-7 are drawn to non-elected species.
Claims 1-14 are pending in the instant application.
Claims 4-7 are withdrawn from further consideration.
Election/Restrictions
Applicant’s election without traverse of claim 2 in the reply filed on 05/26/2026 is acknowledged.
Note, if Applicant’s currently amended claims 4 and 6 were originally presented, claims 4 and 6 would result in requiring a “further comprising” species election of claims 3, 4 and 6, similar to the previous restriction requirement filed on 11/26/2025 of “further comprising” species of claims 2, 4 and 6. In order to refrain from sending another restriction requirement, the first “further comprising” specie (claim 3) is elected for examination purposes.
Note, claims 4 and 6 are drawn to non-elected species, wherein claims 5 and 7 are dependent on withdrawn claims 4 and 6 and are further withdrawn.
Claim Rejections - 35 USC § 112, 1st paragraph
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 1-3, 12, 14 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 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 or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claims 1 and 2, The terms “metabolite” and “prodrugs” do not meet the written description provision of 35 USC § 112, first paragraph, due to lacking chemical structural information for what they are and chemical structures are highly variant and encompass a myriad of possibilities. The specification provides insufficient written description to support the genus of metabolite and prodrugs encompassed by the claim, since there is no description of the structural relationship of these derivatives provided in the specification and Applicant has not provided a description as to how the base molecule may be changed while remaining a metabolite or prodrug.
Regarding claims 1 and 2, the term “radioisotope” makes the claims confusing, because “radiolabeled acetoacetate” means there is a radioisotope attached to the acetoacetate; thus, the additional term of “radioisotope” by itself means a radioisotope is not required to be attached to another molecule, which is broader in scope than “radiolabeled acetoacetate”.
Regarding claims 3, 12 and 14, claims 3, 12, and 14 contain the terms "CMRket" and “CMRtot” and “APOE” and “FDG”, respectively, which is not defined by the claims. Claims must stand alone to define the invention, and should not rely on the description or the drawings to give them meaning (see Ex Parte Fressola, 27 USPQ 2d 1608). Thus, these claims, at the very least, should define "CMRket" and “CMRtot” and “APOE” and “FDG” by its formal name; once ""CMRket" and “CMRtot” and “APOE” and “FDG” are defined, the terms "CMRket" and “CMRtot” and “APOE” and “FDG” may be subsequently recited.
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.
Claim(s) 1-3, 8-14 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by CASTELLANO et al (Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer’s Disease Dementia. Journal of Alzheimer’s Disease 43 (2015) 1343–1353) as evidenced by MCKHANN et al (The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011 May; 7(3): 263–269).
Regarding claims 1, CASTELLANO teaches a method for a disorder in a subject, such as Alzheimer’s Disease (see title and abstract), comprised of: administering a first radiopharmaceutical composition, such as injecting 11C-acetoacetate (see title; abstract; and pg. 1345, under Regional brain PET); and brain 11C-AcAc PET images were analyzed by region of interest (ROI) (see pg. 1345, under Analysis of PET images; and pg. 1349, Fig. 2), which reads on acquiring a first image of an organ of interest. Additional disclosures include: magnetic resonance (MR) imaging were also obtained (see pg. 1344, 2nd col).
CASTELLANO further teaches “the cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer’s disease (AD). The ketones, acetoacetate and B-hydroxybutyrate, are the brain’s main alternative energy substrates to glucose” (see abstract).
Regarding claims 2, CASTELLANO teaches 18F-FDG injection were given (see pg. 1345, 1st col), which reads on administering a second radio pharmaceutical composition to the subject; brain 18F-FDG images were analyzed by region of interest (ROI) (see pg. 1345, under Analysis of PET images; and pg. 1349, Fig. 2), which reads on acquiring a second image of an organ of interest.
Regarding claim 3, CASTELLANO teaches multiple-time graphical analysis was used to calculate the cerebral metabolic rate (CMR) of glucose (CMRg) and acetoacetate (CMRa) (see pg. 1345, 2nd col). Note, Applicant’s recitation of “determining CMRket and CMRtot based on the first and second acquired images” appears to be a mental step, not an active step.
Regarding claim 8-10, CASTELLANO teaches the subject has Alzheimer’s disease (see title and abstract).
Regarding claims 11-12, participants with mild possible or probable AD dementia were diagnosed according to the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimer’s Disease and Related Disorders Association (ADRDA) criteria (see pg. 1344, 2nd col), which is reference #22 (MCKHANN et al). MCKHANN teaches diagnosis of dementia due to Alzheimer’s disease guideline (see title), such as probable AD dementia in a carrier of a causative AD genetic mutation (see pg. 5, at 4.2.2), which reads on genetic markers.
Claim Rejections - 35 USC § 103
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 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.
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.
Claim(s) 1-3, 8-13 is/are rejected under 35 U.S.C. 103 as being unpatentable over CASTELLANO et al (Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer’s Disease Dementia. Journal of Alzheimer’s Disease 43 (2015) 1343–1353) as evidenced by MCKHANN et al (The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011 May; 7(3): 263–269) in view of BLOMQVIST et al (Use of R-~-[1- 11C]hydroxybutyrate in PET studies of regional cerebral uptake of ketone bodies in humans. Am. J. Physiol. 269 (Endocrinol. Metab. 32): E948-E959, 1995).
As discussed above, the references teach Applicant’s invention, wherein emphasis is on CASTELLANO teaching “the cerebral metabolic rate of glucose (CMRg) is lower in specific brain regions in Alzheimer’s disease (AD). The ketones, acetoacetate and B-hydroxybutyrate, are the brain’s main alternative energy substrates to glucose” (see abstract), wherein CASTELLANO’s examples were based on radiolabeled acetoacetate, such as 11C-acetoacetate (see title).
Regarding claim 13, the references do not teach using radiolabel B-hydroxybutyrate (BHB), such as 11C-BHB.
BLOMQVIST teaches the prior art had known of radiolabel 11C-B-hydroxybutyrate used in PET studies of regional cerebral uptake of ketone bodies (see title; and abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate radiolabeling the B-hydroxybutyrate (BHB) with 11C, such as 11C-BHB. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because acetoacetate and B-hydroxybutyrate are functional equivalents of ketones that are known to be the brain’s main alternative energy substrates to glucose.
Claim(s) 1-3, 8-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over CASTELLANO et al (Lower Brain 18F-Fluorodeoxyglucose Uptake But Normal 11C-Acetoacetate Metabolism in Mild Alzheimer’s Disease Dementia. Journal of Alzheimer’s Disease 43 (2015) 1343–1353) as evidenced by MCKHANN et al (The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011 May; 7(3): 263–269) in view of MATTINGLY et al (Synthesis and in vivo evaluation of a radiofluorinated ketone body derivative. RSC Med. Chem. 2020, 11, pg. 297-306).
As discussed above, the references teach Applicant’s invention.
Regarding claim 14, the reference not teach radiolabeling 18F-beta-hydroxybutyrate (18F-BHB).
MATTINGLY teaches the prior art had known of using 18F-beta-hydroxybutyrate (18F-BHB) for studying ketone body metabolism using positron emission tomography (PET) (see abstract). Additional disclosures include: The ketone bodies beta-hydroxybutyric acid and acetoacetic acid represent the principal oxidative energy sources of most tissues when dietary glucose is scarce (see abstract); Alzheimer’s disease (see abstract).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate 18F-BHB. The person of ordinary skill in the art would have been motivated to make those modifications, because it would allow another tool for studying ketone body metabolism using positron emission tomography (PETI
and reasonably would have expected success because the references dealt in the same field of endeavor, such as PET imaging and Alzheimer’s disease.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAKE MINH VU whose telephone number is (571)272-8148. The examiner can normally be reached Mon-Fri 9:00am-5:30pm.
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/JAKE M VU/Primary Examiner, Art Unit 1618
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