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 is a 371 of PCT/EP2022/055775 03/07/2022. Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. UK-2103211.5, filed on 03/08/2021.Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Status of Claims
Claims 1-12, and 14-21 are pending and under examination.
Any rejection found in the previous Office Action and not presented herein has been withdrawn based upon Applicant’s amendments.
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.
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.
Claim(s) 1-12, and 14-19 remain rejected and newly added claims 20-21 are newly rejected under 35 U.S.C. 103 as being unpatentable over Congreve, M. S., et. al. (US Patent No. 10,030,035 B2; Issued 07/24/2018) (partially newly applied as necessitated by amendment).
Congreve teaches the Applicant’s claimed compound, ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See e.g. col. 26; Table 1; Example 2-2) encompassing both stereoisomers as claimed in claims 2 and 3, and having activity as muscarinic M1 and M4 receptor agonists at higher selectivity than M2 and M3 receptors (See e.g. col. 3; line 66- col.4; line 3). Congreve also teaches that this mechanism is relevant in Alzheimer’s Disease and dementia (See e.g. col. 1; lines 40-61), that ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate is administered to human subjects in need thereof (See e.g. col. 26; line 4), claims a method of treating dementia in a subject in need thereof using ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See claim 10), and mentions that the dementia may be dementia with Lewy bodies (See e.g. col. 18; Line 57).
Congreve also teaches that the claimed compound can be further converted into a pharmaceutically acceptable salt (See e.g. col. 84; lines 5). Congreve also teaches that the claimed compound can be in a composition with pharmaceutically acceptable excipients such as, “carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents (e.g solid diluents such as fillers or bulking agents; and liquid diluents such as solvents and co-solvents), granulating agents, binders, flow aids, coating agents, release-controlling agents (e.g. release retarding or delaying polymers or waxes), binding agents, disintegrants, buffering agents, lubricants, preservatives, anti-fungal and antibacterial agents, antioxidants, buffering agents, tonicity-adjusting agents, thickening agents, flavouring agents, sweeteners, pigments, plasticizers, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions”(See e.g. col. 24; lines 29-41).
Congreve also teaches that the claimed compound can be in a pharmaceutically acceptable dosage form suitable for oral administration, such as “tablets (coated or uncoated), capsules (hard or soft shell), caplets, pills, lozenges, syrups, solutions, powders, granules, elixirs and suspensions, sublingual tablets, wafers or patches such as buccal patches (See e.g. col. 24; lines 60-64).
Congreve provides sufficient teaching, suggestion, and motivation to one having ordinary skill in the art, before the Applicant’s effective filling date, to modify Congreve’s teaching of the Applicant’s claimed compound and stereoisomers, it’s mechanism as a muscarinic M1 and M4 receptor agonist, and that this mechanism is relevant in treating Alzheimer’s Disease and dementia with or without Lewy bodies, to arrive at the Applicant’s claimed method of using ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, in a composition formulated as an oral tablet with pharmaceutically acceptable salts, carriers, and excipients, to treat Alzheimer’s Disease or dementia with or without Lewy bodies in a human subject.
Congreve also teaches that the pharmaceutical compositions may contain a sufficient amount of ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate to provide a desired level of biological activity, and may contain between 1 nanogram to 2 grams of the claimed compound, and that oral dosage forms may contain 1 mg to 2 g, or preferably 10 mg to 1g (See e.g. col. 25; line 54 - col. 26; line 2).
According to MPEP 2144.05, "In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)".
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical."[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Congreve also teaches donepezil as an alternative cholinesterase inhibitor serving as a positive control from which to compare the effects of ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See e.g. col. 87; line 35-38).
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
While Congreve does not teach the Applicant’s specific dose of 10mg of donepezil, this amount would have been arrived at by one having ordinary skill in the art, as donepezil is taught to be a cholinesterase inhibitor, a result-effective variable that serves as a basis from which one having ordinary skill in the art would be expected to arrive at the instant dose through routine experimentation (MPEP 2144.05 – II).
In the instant case, Congreve provides sufficient teaching, suggestion, and motivation to one having ordinary skill in the art, before the Applicant’s effective filing date, to arrive at a method of treating Alzheimer’s Disease or dementia in a human subject suffering from Alzheimer's Disease or dementia, comprising administering to the subject a pharmaceutical composition comprising ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof, at doses between 5mg and 25 mg, with pharmaceutically acceptable carriers and excipients, in a tablet for oral administration, in combination with donepezil, to treat Alzheimer’s Disease or dementia with or without Lewy bodies in a human subject.
One having ordinary skill in the art, before the Applicant’s effective filing date, would have been motivated and have had reasonable expectation of success in using the Applicant’s compound, ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, taught by Congreve to be used in treating Alzheimer’s and dementia with or without lewy bodies, in comparable dosing ranges, formulated as an oral tablet with pharmaceutically acceptable salts along with pharmaceutically acceptable carriers and excipients, in combination with donepezil.
Therefore, it would have been obvious to one having ordinary skill in the art, before the Applicants effective filing date, to modify Congreve’s teaching and arrive at a method of treating Alzheimer’s Disease or dementia with or without lewy bodies in a human subject suffering from Alzheimer's Disease or dementia, comprising administering to the subject a pharmaceutical composition comprising ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof, at doses between 5mg and 25 mg, with pharmaceutically acceptable carriers and excipients, in a tablet for oral administration, in combination with donepezil to treat Alzheimer’s Disease or dementia with or without Lewy bodies in a human subject.
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 1-12, and 14-19 remain rejected and newly added claims 20-21 are newly rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. US12202843B2 (partially newly applied as necessitated by amendment). Although the claims are not identical, they are not patentably distinct from one another because the claims of US12202843B2 are also drawn to the same compound and method of the instant application, with comparable and obvious limitations such as formulation modifications, using the claimed compound in a comparable method, and obvious dosing regimens and routes of administration. The US12202843B2 claims 1-17 are all drawn to the same compound of the instant Applicant and formulations thereof, used in comparable methods of administration to a subject with Alzheimer’s or dementia. Notable limitations in the method of the Applicant that is not in that of US12202843B2 include oral dosing, and the specific doses of the claimed compound in combination with donepezil, including load doses and daily doses.
However, these limitations are not patentably distinct, as further explained below.
Congreve teaches the Applicant’s claimed compound, ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See e.g. col. 26; Table 1; Example 2-2) encompassing both stereoisomers as claimed in claims 2 and 3, and having activity as muscarinic M1 and M4 receptor agonists at higher selectivity than M2 and M3 receptors (See e.g. col. 3; line 66- col.4; line 3). Congreve also teaches that this mechanism is relevant in Alzheimer’s Disease and dementia (See e.g. col. 1; lines 40-61), that ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate is administered to human subjects in need thereof (See e.g. col. 26; line 4), claims a method of treating dementia in a subject in need thereof using ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See claim 10), and mentions that the dementia may be dementia with Lewy bodies (See e.g. col. 18; Line 57).
Congreve also teaches that the claimed compound can be further converted into a pharmaceutically acceptable salt (See e.g. col. 84; lines 5). Congreve also teaches that the claimed compound can be in a composition with pharmaceutically acceptable excipients such as, “carriers (e.g. a solid, liquid or semi-solid carrier), adjuvants, diluents (e.g solid diluents such as fillers or bulking agents; and liquid diluents such as solvents and co-solvents), granulating agents, binders, flow aids, coating agents, release-controlling agents (e.g. release retarding or delaying polymers or waxes), binding agents, disintegrants, buffering agents, lubricants, preservatives, anti-fungal and antibacterial agents, antioxidants, buffering agents, tonicity-adjusting agents, thickening agents, flavouring agents, sweeteners, pigments, plasticizers, taste masking agents, stabilisers or any other excipients conventionally used in pharmaceutical compositions”(See e.g. col. 24; lines 29-41).
Congreve also teaches that the claimed compound can be in a pharmaceutically acceptable dosage form suitable for oral administration, such as “tablets (coated or uncoated), capsules (hard or soft shell), caplets, pills, lozenges, syrups, solutions, powders, granules, elixirs and suspensions, sublingual tablets, wafers or patches such as buccal patches (See e.g. col. 24; lines 60-64).
Thus far, Congreve provides sufficient teaching, suggestion, and motivation to one having ordinary skill in the art, before the Applicant’s effective filling date, to modify Congreve’s teaching of the Applicant’s claimed compound and stereoisomers, it’s mechanism as a muscarinic M1 and M4 receptor agonist, and that this mechanism is relevant in treating Alzheimer’s Disease and dementia with or without Lewy bodies, to arrive at the Applicant’s claimed method of using ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate, in a composition formulated as an oral tablet with pharmaceutically acceptable salts, carriers, and excipients, to treat Alzheimer’s Disease or dementia with or without Lewy bodies.
Congreve also teaches that the pharmaceutical compositions may contain a sufficient amount of ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate to provide a desired level of biological activity, and may contain between 1 nanogram to 2 grams of the claimed compound, and that oral dosage forms may contain 1 mg to 2 g, or preferably 10 mg to 1g (See e.g. col. 25; line 54 - col. 26; line 2).
According to MPEP 2144.05, "In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990)".
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical."[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
Congreve also teaches donepezil as an alternative cholinesterase inhibitor serving as a positive control from which to compare the effects of ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8-azabicyclo[3.2.1]octane-8-carboxylate (See e.g. col. 87; line 35-38).
"It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
While Congreve does not teach the Applicant’s specific dose of 10mg of donepezil, this amount would have been arrived at by one having ordinary skill in the art, as donepezil is taught to be a cholinesterase inhibitor, a result-effective variable that serves as a basis from which one having ordinary skill in the art would be expected to arrive at the instant dose through routine experimentation (MPEP 2144.05 – II).
In the instant case, Congreve provides sufficient teaching, suggestion, and motivation to one having ordinary skill in the art, before the Applicant’s effective filing date, to arrive at a method of treating Alzheimer’s Disease or dementia in a human subject suffering from Alzheimer's Disease or dementia, comprising administering to the subject a pharmaceutical composition comprising ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof, at doses between 5mg and 25 mg, with pharmaceutically acceptable carriers and excipients, in a tablet for oral administration, in combination with donepezil, to treat Alzheimer’s Disease or dementia with or without Lewy bodies in a human subject.
One having ordinary skill in the art, before the Applicant’s effective filing date, would have been motivated and have had reasonable expectation of success in using the Applicant’s compound, ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, taught by Congreve to be used in treating Alzheimer’s and dementia with or without lewy bodies, in comparable dosing ranges, formulated as an oral tablet with pharmaceutically acceptable salts along with pharmaceutically acceptable carriers and excipients, in combination with donepezil.
Therefore, it would have been obvious to one having ordinary skill in the art, before the Applicants effective filing date, to modify Congreve’s teaching and arrive at a method of treating Alzheimer’s Disease or dementia with or without lewy bodies in a human subject suffering from Alzheimer's Disease or dementia, comprising administering to the subject a pharmaceutical composition comprising ethyl 3-(3-oxo-2,8-diazaspiro[4.5]dec-8-yl)-8- azabicyclo[3.2.1]octane-8-carboxylate, or a pharmaceutically acceptable salt thereof, at doses between 5mg and 25 mg, with pharmaceutically acceptable carriers and excipients, in a tablet for oral administration, in combination with donepezil to treat Alzheimer’s Disease or dementia with or without Lewy bodies in a human subject.
It would have been prima facie obvious to one skilled in the art to arrive at the Applicant’s instant claims, in view of the claims of U.S. Patent No. US12202843B2, and Congreve, M. S., et. al. (US Patent No. 10,030,035 B2; Issued 07/24/2018).
Response to Arguments
Applicant’s arguments filed 4/23/2026 have been fully considered, but they are not persuasive.
Applicant is traversing Examiner’s previously set forth 35 U.S.C. 103 rejection over claims 1-12, and 14-19, and has added new claims 20 and 21 which have been included in the rejection maintained above due to being equivalent in scope as the previously rejected claims.
Traversal of the 35 U.S.C. 103 rejection of claims 1-12, and 14-19
Applicant’s arguments of unexpected results have been considered by the examiner. Unexpected results must be shown as compared to the closest prior art. In this instance, the unexpected result being alleged appears to be administration of the claimed agent for treating Alzheimer’s disease and/or dementia. Applicant points to Examples C and D wherein a dose of 15 mg to 25 mg was administered to a subject with mild to moderate AD. The results show tolerability and efficacy.
The examiner notes that unexpected results have not been shown in the form of a critical concentration range. To do so would require a showing of an unexpected advantage of 15 to 25 mg as compared to those dosages outside of the claimed range. There has been no showing in this regard. With respect to a method of administering the active agent itself, the closest prior art teaches administration of the claimed agent to the same subject population (i.e., a subject with dementia and/or AD). As such, it is not clear how such showing is unexpectedly advantageous as compared to the same active step of administration. Efficacy and relative safety is expected as the claimed compound would not be claimed for use in a method of administration to a human subject if it was not safe and effective. As such, unexpected results have not been established and the examiner is determining if a prima facie showing is set forth on the record.
In regards to Applicants argument that no explanation or rationale was provided as to why Example 2-2 of Congreve would be selected by one having ordinary skill in the art to further develop into a pharmaceutical composition:
Congreve, while disclosing the Applicant's select species, also discloses that a broader genus of the compounds are agonists of the muscarinic M1 receptor and are useful in the treatment of muscarinic M1 receptor mediated diseases (See Page 1; Abstract). Congreve then also teaches that the compounds of this genus exhibit particular specificity for M1 and M4 receptor subtypes, over the M2 and M3 receptor subtypes (See Column 3; Lines 55-58)
At this point, one having ordinary skill in the art, prior to the Applicant's effective filing date, would have appreciated the specificity of the genus of compounds taught by Congreve to address and treat diseases that are particularly mediated by the M1 and M4 receptor subtypes. Congreve further provides a nexus between the genus of compounds, their specificity for the M1 and M4 receptor subtypes, and an application to Alzheimer's Disease and dementia, by the recitation:
"In particular, the invention is directed to a class of compounds, which are agonists of the muscarinic M1 and/or M4 receptor, and hence useful in the treatment of Alzheimer's Disease, schizophrenia, cognitive disorders and other diseases mediated by the muscarinic M1/M4 receptors, as well as the alleviation of pain"(See Column 1; Lines 12-20).
Further, Congreve teaches that of the five muscarinic receptor subtypes, M2 receptors while present in the CNS, also reside in cardiac tissue, where they mediate vagal innervation of the heart, as well as in smooth muscle and exocrine glands (See Column 1; Lines 30-37), and that M3 receptor subtypes are expressed at relatively low levels in the CNS, but are prevalent in smooth muscle and glandular tissues (See Column 1; Lines 37-40). Through these teachings, Congreve provides teaching, suggestion, and motivation to one having ordinary skill in the art, before the Applicant's effective filing date, to avoid agonizing M2 and M3 receptor subtypes due to their potential for off-target effects and irrelevance in addressing CNS issues such as Alzheimer's or dementia, and instead target the M1/M4 receptors.
As to why one having ordinary skill in the art would choose the Applicant's compound specifically:
Example compound 2-2, Congreve discloses a TABLE 4, wherein a list of species of Congreve's genus of compounds are provided with activity in terms of pEC50 for M1, M2, M3, and M4 receptors. Of this list, roughly half show no test data for activity at the M2 and M3 receptors. Of the remaining species that do test for activity at M2 and M3 receptors, Example 2-2 has the lowest activity at the M2 and M3 receptors, with percentage Emax of acetylcholine at around zero, while simultaneously maintaining some of the highest activity at the M1 and M4 receptors when compared to the rest of the species of TABLE 4. As explained before, agonizing M1 and M4 receptors while avoiding M2 and M3 receptors is advantageous when considering a compound for the treatment of Alzheimer's or dementia. It should be noted that Congreve also elects Applicants compound, Example 2-2, to use in an Example B study, wherein the Applicant's compound was found to reverse scopolamine induced amnesia (See Column 87; Example B).
This in fact provides strong motivation to one having ordinary skill in the art, before the Applicant's effective filing date, to specifically choose the Applicant's compound, Example 2-2, to further develop into a pharmaceutical composition with the intent of administering the composition to a subject suffering from Alzheimer's Disease or dementia, for which the motivation was set forth above.
In regards to the Applicant's argument that the dosage taught by Congreve is overly broad, such that one having ordinary skill in the art, before the Applicant's effective filing date, would have a difficult time arriving at the instantly claimed dosing ranges, Examiner acknowledges that the ranges taught by Congreve are much broader than the that of the Applicant. However, these ranges serve as a basis for one having ordinary skill in the art to routinely optimize dosing according to the specific traits of the subject of the treatment method.
As Congreve has successfully established a result-effective variable, wherein increased agonism of the M1 and M4 receptor subtypes through binding of the Applicant's compound results in the effect of reduced Alzheimer's Disease and dementia symptoms, one having ordinary skill in the art, through routine and undue experimentation, would have arrived at the claimed dosing of the Applicant (MPEP 2144.05). Thus, as currently understood by Examiner, it would have been obvious and within the realm of undue experimentation, for one having ordinary skill in the art, before the Applicant's effective filing date, to determine the optimal dose for a given subject of the method.
However, if Applicant intends to claim unexpected results around the particular dosing claimed, such that one having ordinary skill in the art would not have been reasonably expected to arrive at the Applicant's specific dosing, Examiner asks for Applicant to make this known on record, and provide commensurate disclosure and rationale as to what in particular about the specific dosing amounts, for both load dose and daily dose, results in an unexpected outcome, such as identifying a threshold for treatment wherein dosing outside of the 5mg -25mg range would not be expected to work.
Similarly, donepezil taught by Congreve to be a positive control and direct comparator to the Applicants instant compound (See Column 87; Example B) solidifies its place in the art as a known treatment of Alzheimer's Disease or dementia, and thus would be obvious to administer in combination with the Applicant's compound, taught previously to be obvious for its advantageous use in Alzheimer's Disease. If Applicant intends to claim an unexpected result from the combination of the Applicants compound and donepezil, such that one having ordinary skill in the art could not have reasonably arrived at the unexpected result of the combination, Examiner asks that Applicant make this known on record, and provide commensurate disclosure and rationale as to what result of the combination was unexpected.
Examiner acknowledges the experiments of the Applicant. However, it is not readily apparent that these data elucidated by the Applicant are unexpected over the art. Absent of any apparent unexpected results over what was previously understood in the art, any characterization of the instantly claimed method is merely considered previously unappreciated property.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP § 2112.01 with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103.
Applicant’s arguments are not persuasive. Examiner maintains the full-scope of the previously set forth rejection of claims 1-12, and 14-19, and further rejects newly added claims 20 and 21.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 OROD MOTEVALLI whose telephone number is (571)272-6026. The examiner can normally be reached Monday - Friday 10:00AM - 6:00PM.
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, Amy L Clark can be reached at (571) 272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/OROD MOTEVALLI/Examiner, Art Unit 1628
/AMY L CLARK/Supervisory Patent Examiner, Art Unit 1628
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