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 .
Status of Claims
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are pending in the instant application. Claims 9, 18, 21, 25-27, 34, 40-42, 48, 57, 60 and 66 are amended and claims 6-8, 10-17, 19-20, 22-24, 28-32, 35-39, 43-47, 49-56, 58-59, 61-65 and 67-71 are cancelled via the amendment filed 03/20/2024.
Information Disclosure Statement (IDS)
The Information Disclosure Statement filed March 20th, 2024 was considered by the Examiner.
Claim Rejections - 35 USC § 112(a)
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 1-5, 9 18, 21 and 25-27 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling a method of slowing the progression of cognitive impairment and reducing the rate of cognitive decline in an APOE4 non-carrier subject, does not reasonably provide enablement for preventing the progression of cognitive impairment or preventing the development of cognitive decline in an APOE4 non-carrier. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). These include: (1) breadth of the claims; (2) nature of the invention; (3) state of the prior art; (4) amount of direction provided by the inventor; (5) the level of predictability in the art; (6) the existence of working examples; (7) quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (8) relative skill in the art. All of the factors have been considered with regard to these claims, with the most relevant factors discussed below:
1) The breadth of claims: The instant claims are directed to a method of preventing or slowing the progression of cognitive impairment or preventing the development or reducing the rate of cognitive decline in an APOE4 non-carrier. This is a very broad claim, one that is not supported by the instant specification.
2) The nature of the invention: The nature of the invention is to a method of preventing or slowing the progression of cognitive impairment or preventing the development or reducing the rate of cognitive decline in an APOE4 non-carrier. Currently, there are no known agents that even treat all cognitive impairments, let alone prevent them. Alzheimer’s disease, a cognitive impairment is still, at present uncurable, as evidenced by Li et al (Neurol Ther. 2023 Feb;12(1):39-72, Epub 2022 Nov 14.).
3) The state of the prior art: The state of the art is very high in terms of compositions comprising a drug for slowing the progression of cognitive impairment or reducing the rate of cognitive decline. However, there is no evidence in the prior art that the instant composition would prevent the progression of cognitive impairment or the development of cognitive impairment.
4) The amount of direction provided by the inventor: There is nothing in the specification that would indicate that the current invention prevents the progression of cognitive impairment or prevents the development of cognitive decline in an APOE4 non-carrier. The method of slowing the progression of cognitive impairment and reducing the rate of cognitive decline in an APOE4 non-carrier subject is a very broad claim. However, there is a substantial gap between treatment and prevention. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap.
5) Predictability of the art: Prevention of the progression of cognitive impairment or the development of cognitive decline in an APOE4 non-carrier is highly unpredictable due to the numerous sources that could trigger cognitive impairment.
6) The presence or absence of working examples: Applicant has some examples of administering the composition to patients with mild cognitive impairment due to Alzheimer’s disease, none of which teaches how to prevent the progression of cognitive impairment or prevent the development of cognitive decline in an APOE4 non-carrier. Overall, applicant fails to provide examples showing that the instant method could kill a progenitor or a stem cell or a cancer stem cell or prevent a disorder associated with Arf1 activity. Therefore, the practitioner would turn to trial and error experimentations to make/use the instant compositions for preventing the progression of cognitive impairment or preventing the development of cognitive decline in an APOE4 non-carrier from the specification or the prior art.
7) The quantity of experimentation: In the instant case, there is a substantial gap between treatment and prevention. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap. In order to utilize the composition as claimed, the skilled artisan would be presented with an inordinate degree of experimentation, having an unpredictable outcome. An undetermined number of experimental factors utilizing a system for preventing the progression of cognitive impairment or preventing the development of cognitive decline in an APOE4 non-carrier would have to be resolved by the practitioner and/or the patient. As indicated in MPEP 2164.03, The "predictability or lack thereof" in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention. The disclosure is not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
8) The relative skill of those in the art: the skill of one of ordinary skill in the art is high, e.g. Ph.D. and M.D. level skill.
In summation, Applicant does not reasonably provide enablement for preventing the progression of cognitive impairment or preventing the development of cognitive decline in an APOE4 non-carrier.
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 and 18 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022).
Regarding claim 1, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Wang also teaches that the AGB101 has been developed as a novel extended release formulation of low dose levetiracetam for slowing the progression of amnestic mild cognitive impairment (detailed description). Wang further teaches that it is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns (detailed description).
Regarding claim 18, as seen above, Wang teaches that AGB101 is low dose levetiracetam in an extended release formulation.
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.
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, 9, 18, 21 and 25-27 is/are rejected under 35 U.S.C. 103 as being unpatentable over (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022) in view of Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Regarding claim 1, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Wang also teaches that the AGB101 has been developed as a novel extended release formulation of low dose levetiracetam for slowing the progression of amnestic mild cognitive impairment (detailed description). Wang further teaches that it is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns (detailed description).
Regarding claim 18, as seen above, Wang teaches that AGB101 is low dose levetiracetam in an extended release formulation.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art is deemed to anticipate instant claims 1 and 18 where anticipation is the epitome of obviousness. In re Pearson, 494 F.2d 1399, 1402 (CCPA 1974)).
Wang does not explicitly teach that the subjects carry a genetic risk factor or presents with cognitive performance below the normal range for their age. Wang also does not explicitly indicate the additional contents of the levetiracetam composition.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Gallagher teaches a method of treating cognitive impairment with an extended release pharmaceuticals composition of levetiracetam (abstract). As both Wang and Gallagher teach a method of treating cognitive impairment with levetiracetam, one of ordinary skill in the art would have been motivated to alter the teachings of Wang with the teachings of Gallagher.
Regarding claim 2, Gallagher teaches that the method of administering the pharmaceutical composition comprising levetiracetam is to treat cognitive impairment in a subject in need of or at risk thereof (abstract). Gallagher also teaches that this may be at the result of genetics (column 26, paragraph 1). Thus, as Wang teaches the administration of levetiracetam for the treatment of memory function in APOE4 non-carriers and Gallagher teaches the administration of levetiracetam for treating cognitive impairment one of ordinary skill in the art would have been motivated to administer the composition to those with genetic risk of developing cognitive impairment as Gallagher includes subjects who are at risk thereof.
Regarding claim 3, Gallagher teaches that cognitive impairment may refer to subjects affected by aged-related cognitive impairment, which refers to cognitive function in subjects that is not as robust as that expected in an aged-matched normal, unimpaired subject, or the function of a young adult subject (column 7, paragraph 6).
Regarding claim 9, Gallagher teaches that the method includes the treatment of mild cognitive impairment (claim 21).
Regarding claim 21, Gallagher teaches that the pharmaceutical composition administered in the method of treating cognitive impairment comprises 220 mg of levetiracetam, 347.5 mg of hydroxypropyl methylcellulose, 1.4 mg of colloidal silicon dioxide, 119.2 mg of silicified microcrystalline cellulose and 6.7 mg of magnesium, stearate (claim 22).
Regarding claim 25, Gallagher teaches that the hydroxypropyl methylcellulose is Hypromellose 2208 (claim 23).
Regarding claim 26, Gallagher teaches that the silicified microcrystalline cellulose is silicified microcrystalline cellulose SMCC 90 (claim 25).
Regarding claim 27, Gallagher teaches that the preferred steady state formula is between 1.9 and 4.4 μg/mL (column 39, paragraph 4).
Claim(s) 1, 4-5, 18, 33-34, 42 and 57 is/are rejected under 35 U.S.C. 103 as being unpatentable over (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022) in view of Du et al (Neurobiology of Aging 27 (2006) 733–740).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Regarding claim 1, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Wang also teaches that the AGB101 has been developed as a novel extended release formulation of low dose levetiracetam for slowing the progression of amnestic mild cognitive impairment (detailed description). Wang further teaches that it is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns (detailed description).
Regarding claim 18, as seen above, Wang teaches that AGB101 is low dose levetiracetam in an extended release formulation.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art is deemed to anticipate instant claims 1 and 18 where anticipation is the epitome of obviousness. In re Pearson, 494 F.2d 1399, 1402 (CCPA 1974)).
Wang does not explicitly teach that the APOE4 non-carrier subjects present with or displays with volumetric atrophy of a subregion of the medial temporal lobe.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Wang further teaches that the inclusion criteria for the study includes normal cognitive function (criteria).
Further, Du teaches that cognitively normal subjects often display entorhinal cortex and hippocampal atrophy rates that are significantly greater than zero (page 734, right column, paragraph 1).
Regarding claims 4-5, as Wang teaches the administration of levetiracetam to APOE4 non-carriers to improve memory, wherein the inclusion criteria for the subjects include cognitively normal subjects, one of ordinary skill in the art would recognize that the subjects also have atrophy in the entorhinal cortex as Du teaches that cognitively normal subjects often display entorhinal cortex and hippocampal atrophy rates that are significantly greater than zero.
Regarding claim 33, one of ordinary skill in the art would have been motivated to administer levetiracetam as a method for delaying or reducing the ate of volumetic atrophy of a subregion of the medial temporal lobe in an APOE4 non-carrier subject and would have a reasonable expectation of success as Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily, to APOE4 non-carriers that are cognitively normal and Du teaches that cognitively normal subjects often display entorhinal cortex and hippocampal atrophy rates that are significantly greater than zero.
Regarding claims 34 and 42, as seen above, Du teaches that the atrophy is in the ERC.
Regarding claim 57, as seen above, Wang teaches that AGB101 is low dose levetiracetam in an extended release formulation.
Claim(s) 1, 4-5, 18, 33-34, 40-42, 48, 57, 60 and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022) in view of Du et al (Neurobiology of Aging 27 (2006) 733–740), as applied to claims 1, 4-5, 18, 33-34, 42 and 57 and in further view of Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Regarding claim 1, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Wang also teaches that the AGB101 has been developed as a novel extended release formulation of low dose levetiracetam for slowing the progression of amnestic mild cognitive impairment (detailed description). Wang further teaches that it is known that age and the APOE 4 gene are important risk factors for late-onset Alzheimer's disease. Further studies have shown that cognitively normal, older adults have more hyperfunctional brain network activity, increased alpha beta accumulation, decreased memory function, and decreased brain volume, which is consistent with Alzheimer's disease patterns (detailed description).
Regarding claim 18, as seen above, Wang teaches that AGB101 is low dose levetiracetam in an extended release formulation.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art is deemed to anticipate instant claims 1 and 18 where anticipation is the epitome of obviousness. In re Pearson, 494 F.2d 1399, 1402 (CCPA 1974)).
Neither Wang nor Du explicitly teach that the subjects carry a genetic risk factor or presents with cognitive performance below the normal range for their age, nor explicitly indicate the contents of the levetiracetam composition.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
However, Gallagher teaches a method of treating cognitive impairment with an extended release pharmaceuticals composition of levetiracetam (abstract). As both Wang and Gallagher teach a method of treating cognitive impairment with levetiracetam, one of ordinary skill in the art would have been motivated to alter the teachings of Wang with the teachings of Gallagher.
Regarding claim 40, Gallagher teaches that the method of administering the pharmaceutical composition comprising levetiracetam is to treat cognitive impairment in a subject in need of or at risk thereof (abstract). Gallagher also teaches that this may be at the result of genetics (column 26, paragraph 1). Thus, as Wang teaches the administration of levetiracetam for the treatment of memory function in APOE4 non-carriers and Gallagher teaches the administration of levetiracetam for treating cognitive impairment one of ordinary skill in the art would have been motivated to administer the composition to those with genetic risk of developing cognitive impairment as Gallagher includes subjects who are at risk thereof.
Regarding claim 41, Gallagher teaches that cognitive impairment may b refer to subjects affected by aged-related cognitive impairment, which refers to cognitive function in subjects that is not as robust as that expected in an aged-matched normal, unimpaired subject, or the function of a young adult subject (column 7, paragraph 6).
Regarding claim 48, Gallagher teaches that the method includes the treatment of mild cognitive impairment (claim 21).
Regarding claim 60, Gallagher teaches that the pharmaceutical composition administered in the method of treating cognitive impairment comprises 220 mg of levetiracetam, 347.5 mg of hydroxypropyl methylcellulose, 1.4 mg of colloidal silicon dioxide, 119.2 mg of silicified microcrystalline cellulose and 6.7 mg of magnesium, stearate (claim 22).
Regarding claim 66, Gallagher teaches that the preferred steady state formula is between 1.9 and 4.4 μg/mL (column 39, paragraph 4).
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 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 9, 15, 21, 22, 27, 28, 34, 37, 41, 42, 58, 61, 62 and 64-67 of copending Application No. 18/852,724 (reference application) in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims A method of preventing or slowing the progression of cognitive impairment or preventing the development or reducing the rate of cognitive decline in a subject, the subject displaying or presenting with cognitive performance within the normal range for the subject's age, the method comprising administering to the subject levetiracetam, brivaracetam or seletracetam, or a pharmaceutically acceptable salt thereof at a daily dose of 0.7-350 mg or comprising administering to the subject a pharmaceutical composition comprising the daily dose of the levetiracetam, brivaracetam or seletracetam or pharmaceutical salt thereof and a pharmaceutically acceptable carrier (claim 1).
The copending application does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Regarding claims 1 and 18, as Wang teaches that levetiracetam is useful in treating cognitive impairment in APOE4 non-carriers, one of ordinary skill in the art would have been motivated to alter the method as claimed in the copending application to include patients that are APOE4 non-carriers.
Regarding claim 2, the copending application teaches that the subject shows risk of cognitive impairment in multiple genes (claim 59).
Regarding claim 21, the copending application claims a pharmaceutical composition with hydroxypropyl methylcellulose, colloidal silicon dioxide, silicified microcrystalline cellulose and magnesium sterate (claim 9).
Regarding claim 27, the copending application claims that the levetiracetam, or pharmaceutically acceptable salt thereof, is in a once-a-day extended release form and provides a steady state plasma concentration of levetiracetam in a subject of between 1.9 µg/mL and 4.4 µg/mL within 3 hours after administration and extending for at least 8 hours of a 24-hour period after said administration (claim 15).
Regarding claim 33 and 42, Du teaches that cognitively normal subjects often display entorhinal cortex and hippocampal atrophy rates that are significantly greater than zero (page 734, right column, paragraph 1). Thus, as Wang teaches the administration of levetiracetam to APOE4 non-carriers to improve memory, wherein the inclusion criteria for the subjects include cognitively normal subjects, one of ordinary skill in the art would recognize that the subjects also have atrophy in the entorhinal cortex as Du teaches that cognitively normal subjects often display entorhinal cortex and hippocampal atrophy rates that are significantly greater than zero.
Regarding claim , the copending application teaches that the subject shows risk of cognitive impairment in multiple genes (claim 59).
Regarding claim 60, the copending application claims a pharmaceutical composition with hydroxypropyl methylcellulose, colloidal silicon dioxide, silicified microcrystalline cellulose and magnesium sterate (claim 9).
Regarding claim 66, the copending application claims that the levetiracetam, or pharmaceutically acceptable salt thereof, is in a once-a-day extended release form and provides a steady state plasma concentration of levetiracetam in a subject of between 1.9 µg/mL and 4.4 µg/mL within 3 hours after administration and extending for at least 8 hours of a 24-hour period after said administration (claim 15).
Further, as the copending application claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 24 of copending Application No. 18/376,127 (reference application) in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a pharmaceutical composition comprising levetiracetam, wherein the levetiracetam is present in the composition in an amount of 125mg-250mg.
The copending application does not claim a method of administration of the composition.
However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
As such, one of ordinary skill in the art would have been motivated the administer the composition of the copending application as Wang teaches levetiracetams utility in treating cognitive impairment.
Further, as the copending application claims a composition comprising levetiracetam and the administration of the composition to APOE4 non-carriers for cognitive impairment is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 104, 124 and 180-183 of copending Application No. 18/107,336 (reference application) in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method for treating cognitive impairment associated
with a central nervous system (CNS) disorder in a subject in need or at risk thereof, for delaying
or slowing the progression of said cognitive impairment in the subject, or for reducing the rate of
decline of cognitive function in the subject, in a subject having or at risk of having said cognitive
impairment or decline of cognitive function, the method comprising the step of administering to
said subject a therapeutically effective amount of levetiracetam, or a pharmaceutically acceptable salt, hydrate, solvate, polymorph, or prodrug thereof, at a daily dose of 0.1 mg -350 mg (claim 104).
The copending application does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the copending application claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50, 68, 98, 100-101 of /copending Application No. 17/693,901 (reference application) in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method for treating cognitive impairment associated
with a central nervous system (CNS) disorder in a subject in need or at risk thereof, delaying
or slowing the progression of said cognitive impairment in the subject, or for reducing the rate of
decline of cognitive function in the subject, the method comprising the step of administering to
said subject a therapeutically effective amount of levetiracetam, or a pharmaceutically acceptable salt thereof (claim 50).
The copending application does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the copending application claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 57, 63, 67 and 70 of copending Application No. 17/372,405 (reference application) in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The copending application claims a method for treating cognitive impairment associated
with a central nervous system (CNS) disorder in a subject in need or at risk thereof, comprising administering to the subject levetiracetam in an amount between 0.07mg to 350mg.
The copending application does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the copending application claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 10, 925,834 in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patent claims a method of improving cognition in a subject suffering from cognitive impairment or at risk thereof , wherein the method comrpsies administering An extended release pharmaceutical composition comprising levetiracetam , wherein the composition provides a steady state plasma concentration of levetiracetam in a subject of between 1.9 ug / ml and 4.4 ug / ml within 3 hours after administration and extending for at least 8 hours of a 24 hour period after said administration (claim 5).
The patent does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the patent claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-25 of U.S. Patent No. 10,159,648 in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patent claims A method of treating mild cognitive impairment or amnestic mild cognitive impairment or slowing the progression of mild cognitive impairment or amnestic mild cognitive impairment in a human subject in need thereof , wherein the method comprises administering an oral one -dosage unit , once- a-day pharmaceutical composition , wherein the composition comprises levetiracetam or a pharmaceutically acceptable salt , hydrate , solvate or polymorph thereof , wherein the levetiracetam or the pharmaceutically accept able salt , hydrate , solvate or polymorph thereof in the 45 composition is formulated in a single dosage unit for extended release , and wherein the composition comprises : a ) 190 mg of levetiracetam ; b ) 300 mg of hydroxypropyl methylcellulose ; c ) 1 . 2 mg of colloidal silicon dioxide ; d ) 102 . 8 mg of silicified microcrystalline cellulose or anhydrous dicalcium phosphate ; and e ) 6 mg of magnesium stearate (claim 17).
The patent does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the patent claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
Claims 1-5, 9, 18, 21, 25-27, 33-34, 40-42, 48, 57, 60 and 66 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 8,604,075 in view of Wang et al (NCT03461861, Network-Level Mechanisms for Preclinical Alzheimer’s Disease Development, v.14, published April 28th, 2022), Du et al (Neurobiology of Aging 27 (2006) 733–740), Gallagher et al (US 10,159,648 B2, published December 25th, 2018, as cited on the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The patent a method for treating age-related cognitive impairment in a human subject in need thereof, the method comprising the step of administering to said human subject levetiracetam or a pharmaceutically acceptable salt thereof at a daily dose of 125-250 mg (claim 1).
The patent does not claim that the subject is an APOE4 non-carrier. However, Wang teaches a clinical trial that describes a study protocol for improving memory function (brief summary). Wang teaches the administration of AGB101, low dose levetiracetam extended release formulation at a dose of 220 mg once daily (interventional model description). Wang teaches the administration is to APOE 4 non-carriers (baseline characteristics).
Further, as the patent claims a method of treating cognitive impairment with levetiracetam and the administration of the composition to APOE4 non-carriers is rendered obvious over Wang, the claims are rejected for the same reasons as listed under the 103 rejections above.
Conclusion
No claim is allowed.
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/A.G.K./ Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/ Supervisory Patent Examiner, Art Unit 1699