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 .
Non-Final Rejection
The Status of Claims:
Claims 1-13 are pending.
Claims 1-13 are rejected.
DETAILED ACTION
1. Claims 1-13 are under consideration in this Office Action.
Priority
2. It is noted that this application is a 371 of PCT/EP2022/081184 11/08/2022 , which ahs a foreign priority document, FRANCE FR2111841 11/08/2021.
Drawings
3. The drawings filed on 5/8/24 are accepted by the examiner.
IDS
4. The IDS filed on 5/8/24 are reviewed by the examiner.
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 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.
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.
Claim 2 is 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 pre-AIA the applicant regards as the invention.
In claim 2, the phrase “is selected from among donepezil, galantamine, rivastigmine, tacrine, or any one of their pharmaceutically-acceptable salts” is recited. This expression is improper because the Markush expression would require a close ended “and “ instead of an open ended “or” at the end. Appropriate correction is required.
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 of this title, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
5. Claims 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Patel et al (Combination Therapy for Alzheimer's Disease, DRUGS & AGING, ADIS INTERNATIONAL LTD, NZ, vol. 28, no. 7, 1 January 2011 (2011-01-01),pages 539-546) in view of Denny et al (WO 2020/232246 Al ).
Determination of the scope and content of the prior art
Patel et al discloses a method of treating Alzheimer’s disease(AD) by a therapy of galantamine combined with memantine and their respective composition,
Furthermore, it teaches that the cholinesterase inhibitors(ChEIs), which include galantamine and rivastigmine (both approved for use in mild to moderate AD) and donepezil (approved for use in mild to severe AD); and the non-competitive NMDA receptor antagonist memantine (approved for use in moderate to severe AD) (see abstract).
Moreover, it teaches a combination therapy (CT) in AD refers to a combination of the noncompetitive NMDA receptor antagonist memantine with any of the ChEIs (see page 541 ,a section of 2.2).
Also, it describes that all patients included in the study were previously taking galantamine 12 mg twice daily (24 mg/day) with meals. Memantine therapy was
titrated to 10 mg twice daily (20 mg/day) in 5mg/week increments (week 1: 5 mg in the evening; week 2: 5 mg twice daily) (see page 544, a left col. at the bottom).
In addition, this observational study revealed
that addition of memantine to treatment of AD with ChEIs significantly altered the trajectory of AD by extending the time to nursing home admission.(see page 543, the right col, the first paragraph).
Lastly, combined therapy in AD seems to be safe and well tolerated, and may represent the current gold standard for treatment of moderate to severe AD and possibly mild to moderate AD as well. (see page 545, the right col. the first paragraph).
The current invention, however, differs from the prior art in that the claimed composition containing a FENM dose for 20 mg/day, the molar ratio between the FENM and at least one acetylcholine esterase inhibitor are unspecified in the prior art.
Denny et al teaches a method of treating a recurrence of depression , comprising administering a therapeutically effective amount of a pharmaceutical composition comprising FENM and a pharmaceutically acceptable salt, to a subject (see page 4 ,lines 29-32).
Pharmaceutical compositions may be presented in unit dose forms containing a predetermined amount of active ingredient per unit dose. Such a unit may contain, for example, 5 ug to 1 g, preferably 1 mg to 700 mg, more preferably 5 mg to 100 mg as in claim 3 (partially) of the present compound, depending on the condition being treated, the route of administration and the age, weight and condition of the patient. Such unit doses may therefore be administered more than once a day. Preferred unit dosage compositions are those containing a daily dose or sub-dose (for administration more than once a day), as herein above recited, or an appropriate fraction thereof, of an active ingredient. Furthermore, such pharmaceutical compositions may be prepared by any of the methods well known in the pharmacy art (see page 39, lines 19-27).
In addition, memantine, a noncompetitive open channel NMDAR antagonist, does not reduce depressive symptoms in patients diagnosed with MDD, but is commonly used to treat moderate to severe confusion (dementia) related to Alzheimer's disease (AD) (see page 3 , lines 4-7).
Ascertainment of the difference between the prior art and the claims
1. The difference between the instant application and the applied Patel et al art is that the Patel et al does not expressly teach the claimed composition containing a FENM dose for 20 mg/day, the molar ratio between the FENM and at least one acetylcholine esterase inhibitor. The deficiencies of the Patel et al is partially cured by the Denny et al.
2. The difference between the instant application and the applied Denny et al art is that the Denny et al does not expressly teach claimed at least one acetylcholine esterase inhibitor selected from among donepezil, galantamine, rivastigmine, tacrine with a specific dosage and the molar ratio between the FENM and at least one acetylcholine esterase inhibitor. The deficiencies of the Denny et al are partially cured by the Patel et al.
Resolving the level of ordinary skill in the pertinent art.
Regarding the Claims 4-6, with respect to the lack of disclosing the claimed dosage of each of donepezil, galantamine, rivastigmine, the Patel prior art does mention a general guidance of taking galantamine 12 mg twice daily (24 mg/day) with meals for the AD treatment although the priorart does not teach the dosage amount of each of donepezil and rivastigmine. However, it is well-known in the pharmaceutical art that a certain amount of the dosage per day can be adjusted depending on the condition being treated, the route of administration and the age, weight and condition of the patient. Therefore, it would have been obvious to the skilled artisan in the art to be motivated to adjust the dosage amount of each of donepezil, galantamine, rivastigmine depending on the patient’s conditions and needs.
This is because the skilled artisan in the art would expect such a modification within the purview of the skilled artisan in the art .
Regarding the Claims 7, 11-13, with respect to the lack of disclosing the claimed molar ratio between the FENM and at least one acetylcholine esterase inhibitor, the prior art are silent about it. However, the limitation of a composition with respect to the molar ratio does not impart patentability to the composition claims when such values are those which would be determined by one of ordinary skill in the art in achieving optimum condition for the particular composition. The molar ratio range between the FENM and at least one acetylcholine esterase inhibitor is well-understood by those of ordinary skill in the art to be a result-effective variable, especially when attempting to control the composition by selecting the optimum molar range between the FENM and at least one acetylcholine esterase inhibitor in the composition. Therefore, it would have been obvious to the skilled artisan in the art to be motivated to control the optimum molar ratio range between the FENM and at least one acetylcholine esterase inhibitor in the composition in the absence of an unexpected result. This is because the skilled artisan in the art would expect such a manipulation to be within the purview of the skilled artisan in the art.
,
Considering objective evidence present in the application indicating obviousness or nonobviousness.
Patel et al discloses expressly the method of treating Alzheimer’s disease(AD) by the use of a therapy of a cholinesterase inhibitor such as galantamine combined with memantine and their respective compositions.
Although Patel et al does not teach that a composition contains 3-(2- fluoroethyl)adamantan-1-amine (FENM) and at least one acetylcholinesterase inhibitor, Patel et al does mention at least the combined therapy of the noncompetitive NMDA receptor antagonist memantine with the cholinesterase inhibitors. Similarly, Denny et al does teach the pharmaceutical composition containing an effective amount of FENM and one or more suitable excipients for the method of treating a recurrence of depression , comprising administering a therapeutically effective amount of a pharmaceutical composition comprising FENM and a pharmaceutically acceptable salt, to the subject. Furthermore, it points out that memantine, a noncompetitive open channel NMDAR antagonist, just like FENM, is commonly used to treat moderate to severe confusion (dementia) related to Alzheimer's disease (AD) (see page 3 , lines 4-7).
Both prior at are commonly related to each other with respect to the method of treating Alzheimer's disease (AD) or a mental disease using a noncompetitive open channel NMDAR antagonist.
So, if the skilled artisan in the art had desired to form a composition containing both of 3-(2- fluoroethyl)adamantan-1-amine (FENM) and at least one acetylcholinesterase inhibitor as an alternative in order to apply for the method of treating AD, it would have been obvious to the skilled artisan in the art before the effective filing date of the claimed invention to be motivated to combine a teaching of Denny’s composition containing FENM with Patel’s cholinesterase inhibitor together in order to achieve a synergic treatment.
This is because the skilled artisan in the art would expect such combined composition to be safe and well tolerated, thereby representing the current gold standard for treatment of moderate to severe AD as guidance shown in the prior art.
Conclusion
Claims 1-13 are rejected.
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/TAYLOR V OH/Primary Examiner, Art Unit 1625 5/30/2026
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