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, filed 10 November, 2022, is a national stage application of PCT/JP2021/017368, filed 6 May, 2021, which claims foreign benefit of Application JP2020-083163, filed 11 May, 2020.
Information Disclosure Statement
Four information disclosure statements (IDS) submitted on 10 November, 2022; 22 May, 2024; 3 June, 2024; and 25 July, 2024 are acknowledged and have been considered.
Status of the Application
Receipt is acknowledged of Applicant’s claimed invention, filed 10 November, 2022, in the matter of Application N° 17/924,447. Said documents have been entered on the record.
Claims 1-27 are canceled. Claims 28-50 are new. No new matter was introduced.
Thus, Claims 28-50 represent all claims currently under consideration.
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 29-32 and 41 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.
Claims 29 and 41 recite “wherein the compound or salt thereof comprises cilostazol.” This language is improper because a compound cannot “comprise” another compound.
While independent Claim 28 recites administering a second dose of a compound to a subject previously administered with a first dose and is understood under its broadest reasonable interpretation, dependent Claims 30-32 introduce ambiguity by reciting a total dose including both the first and second doses, even though Claim 28 does not require administering the first dose. Accordingly, it is unclear how the total dose limitation is satisfied by the claimed method.
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 38 and 46 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.
The claims recite “the subject is not diagnosed with intermittent claudication or stroke.” However, the specification does not reasonably convey to one of ordinary skill in the art that the inventors had possession of methods excluding subjects diagnosed with intermittent claudication or stroke.
To the contrary, the specification describes administration of the compound in subjects having intermittent claudication or stroke, including preferred embodiments directed to use in subjects with undiagnosed intermittent claudication or stroke, or in a subject whose stroke is complicated by MCI (instant Specification, Pg. 12, Para 0045.) Thus, the specification affirmatively teaches use of the compound in subjects having intermittent claudication or stroke, rather than exclusion of such subjects.
The specification does not identify intermittent claudication or stroke as conditions to be excluded from treatment or detection, nor does it provide any rationale or guidance suggesting that subjects diagnosed with intermittent claudication or stroke should be excluded.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 39-46 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more. The claims recite a method comprising detecting a compound and metabolites in a biological sample from a patient and optionally calculating an abundance ratio of a metabolite based on detected amounts. This judicial exception is not integrated into a practical application because the claims are directed to observing and analyzing naturally occurring biological information, namely the presence and relative amounts of a drug and its metabolites in a biological sample from a patent. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because detecting compounds or metabolites in a biological sample and calculating a ratio based on detected amounts represent routine and conventional techniques for analyzing biological samples.
Additionally, Claims 47-50 are rejected under 35 U.S.C. 101 for the same reasons set forth with respect to Claim 39 above. Claim 47, and Claims 48-50 which rely upon it, incorporate the detecting method of Claim 39 and further recite administering the compound to the patient after the detecting step. However, the additional step of administering the compound does not meaningfully limit the judicial exception identified in Claim 39. The claim does not require that the results of the detecting step be used to determine, modify, or otherwise affect the administration of the compound. Thus, the administering step merely follows the detecting step and does not integrate the judicial exception into a practical application. The claims therefore encompass methods in which the detecting step is performed and the compound is administered without regard to the results of the detecting step, such that the detecting step does not meaningfully limit the scope of the claim.
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 28-32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hong (US Patent 7,825,130, published 2 November, 2010 and cited in IDS as WO 2004/075897 A1.)
Regarding Claims 28-32, Hong teaches a method of treating a patient with an Alzheimer’s disease comprising administration of cilostazol and at a daily dosage of 100-400 mg, which may be administered in divided doses (‘130, Abstract, Col 3, Para 2-6.)
Under the broadest reasonable interpretation, each administration of a divided daily dose constitutes a dose, and subsequent administrations correspond to a second dose administered to a subject previously administered a first dose.
As such, Claims 28-32 are anticipated by Hong.
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.
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.
Claims 33-37, 39-45 and 47-50 are rejected under 35 U.S.C. 103 as being unpatentable over Hong (US Patent 7,825,130, published 2 November, 2010 and cited in IDS as WO 2004/075897 A1) as applied to Claims 28-32 above, and further in view of Fu et al. (Journal of Chromatography B, 728: 251-262. 1999, cited in IDS), hereinafter Fu.
The teachings of Hong (2010) are set forth in the above 35 U.S.C. 102 Rejections and
are incorporated herein. Hong teaches a method of treating a patient with an Alzheimer’s disease comprising administration of cilostazol and at a daily dosage of 100-400 mg, which may be administered in divided doses.
Hong fails to explicitly teach the step of detecting the metabolites of cilostazol.
However, Fu teaches the quantitative determination of cilostazol and its metabolites in human plasma. Fu finds that cilostazol is extensively metabolized and that several metabolites are pharmacologically active, specifying OPC-13015 (also known as “3,4-dehydro Cilostazol”) and OPC-1321 (also known as “4’-trans-hydroxy Cilostazol”) as the analytes of interest as they are the major circulating metabolites in human plasma after oral administration of cilostazol (Fu, Abstract, Pg. 258-260, Table 4.)
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, to apply the detection methods of Fu to subjects treated according to Hong in order to monitor the presence and levels of cilostazol and its metabolites. Such monitoring represents routine practice in the art for evaluating drug exposure, metabolism, and pharmacokinetics, and for assessing patient response to treatment.
Fu’s quantitative determination inherently provides measured amounts of the compound and metabolites, from which relative amounts and ratios can be readily calculated using routine mathematical operations. Additionally, it would have been obvious to employ mass spectrometry, including liquid chromatography-mass spectrometry, as the analytical technique for such detection and quantification, as mass spectrometry was a well-established and routinely used method for sensitive and selective analysis of drugs and their metabolites in biological samples such as plasma.
The combination of Hong and Fu therefore represents the application of known analytical techniques to a known treatment method for their established purpose, yielding predictable results, and one of ordinary skill in the art would have had a reasonable expectation of success in doing so.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-9 of U.S. Patent No. 11,925,633.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims teach methods of treating dementia, which encompass Alzheimer’s disease, by administering a composition comprising cilostazol, whereas the instant claims recite treating Alzheimer’s disease by administering cilostazol. It would have been obvious to one of ordinary skill in the art to treat a subset of dementia patients, such as those having Alzheimer’s disease, using cilostazol, including as a single agent rather than in combination, as such modifications represent routine variations in the administration of known therapeutic agents.
Claims 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claim 1 of U.S. Patent No. 9,737,524.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims teach methods of treating mild cognitive impairment (MCI) using cilostazol. MCI represents an earlier stage of cognitive decline on the continuum that includes Alzheimer’s disease. It would have been obvious to one of ordinary skill in the art to apply the same treatment to patients with more advanced cognitive impairment, such as Alzheimer’s disease, as a matter of routine extension of therapy across related disease states.
Claims 28-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over Claims 1-4 of U.S. Patent No. 10,016,409.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims teach administration of cilostazol to patients with mild cognitive impairment to improve interstitial flow, demonstrating that cilostazol was known to affect physiological processes relevant to cognitive disorders. This further supports that use of cilostazol in related conditions such as Alzheimer’s disease would have been obvious.
Communication
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Donna M. Nestor whose telephone number is (703)756-5316. The examiner can normally be reached generally (w/flex): 5:30a-5p EST M-Th.
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/D.M.N./ Examiner, Art Unit 1627
/SARAH PIHONAK/ Primary Examiner, Art Unit 1627