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 .
DETAILED ACTION
This Office Action is in response to Applicant’s Arguments and Amendment filed, 01/08/2026, wherein the Amendment amended claim 14, and cancelled claim 18.
Claims 14-17 and 19-20 are pending.
Priority
This application claims the following priority:
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Election/Restrictions
Applicant elected ADRB2 agonist as the compound, in the reply filed on 06/18/2025.
Claims 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim.
Claims 14-17 are examined on the merits herein.
REJECTIONS WITHDRAWN
The status for each rejection and/or objection in the previous Office Action is set out below.
Specification Objections
Applicant’s amendment to [00903] of the instant specification is sufficient to overcome this objection.
Claim Objections
Applicant’s amendments to claim 14 are sufficient to overcome these objections.
35 U.S.C. § 112(b)
Applicant’s deletion of Xerecept is sufficient to overcome this rejection.
Double Patenting
The terminal disclaimer filed on 01/08/2026, disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of Patent No. 11,266,626, has been reviewed and is accepted. The terminal disclaimer has been recorded.
The terminal disclaimer is sufficient to overcome this rejection.
REJECTIONS—MAINTAINED & MODIFIED
Independent claim 14 has been amended to add the limitations of previous claim 18, and further amended to add the phrase “before treatment” following the term “wherein.” Though the below rejections rely on the same prior art references, they have been modified to address the “before treatment” limitation, and the addition of the subject matter of claim 18 into claim 14..
Support for this limitation can be found in at least [00043], [00055], and [00187] of the instant Specification.
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
(Modified) Claim 14 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by WO 2013/149091 to Freed (published 2013, IDS of 09/02/2022).
Freed teaches a method of treating a neurodegenerative disease, such as Alzheimer’s disease (AD), in a subject by administering phenylbutyric acid (pg. 26, claims 9-10).
The wherein clause in the last three lines of claim 14 does not recite any active steps in which the C99 and amyloid beta (Aß) levels of subjects with and without AD, are measured and determined. The wherein clause recites a property of a subject with Alzheimer’s Disease in comparison to that of a subject without Alzheimer’s Disease.
As evidenced by the instant specification, AD subjects have a higher ratio of C99 to beta-amyloid than subjects without AD. Example 1, beginning on pg. 100 of the instant specification teaches that accumulation of APP-C99 triggers the pathogenesis of Alzheimer disease. “In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate. . .C99 that is then cleaved. . .to generate the beta-amyloid (Aß) found in senile plaques. . .Whereas C99 is normally processed rapidly, it accumulates in cells from AD patient and animal models. . .aberrant APP processing in AD results in the accumulation of . . .C99, which is the fundamental effector of the pathogenesis of AD ([00322]).
Thus, it would reasonably be expected that prior to treatment, a subject with AD (i.e., the subject treated in instant claim 14), would have a higher ratio of C99 to total Aß, than a subject without AD, since accumulation of C99 is a hallmark of AD. See MPEP 2112.02.
Response to Arguments
On pgs. 7 Remarks, Applicant argues that Freed fails to disclose measuring a ratio of C99 to total Aß and administering the phenylbutyric acid to treat neurological disease, and argues that Freed does not identify a patient population with neurodegenerative disease for treatment based on a ratio of C99 to total Aß.
This argument has been fully considered, but is not found persuasive. It is respectfully pointed out that the instant claims do not recite a step of measuring a ratio of C99 to total Aß; although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
As discussed in the above rejection:
The wherein clause in the last three lines of claim 14 does not recite any active steps in which the C99 and amyloid beta (Aß) levels of subjects with and without AD, are measured and determined. The wherein clause recites a property of a subject with Alzheimer’s Disease in comparison to that of a subject without Alzheimer’s Disease.
As evidenced by the instant specification, AD subjects have a higher ratio of C99 to beta-amyloid than subjects without AD. Example 1, beginning on pg. 100 of the instant specification teaches that accumulation of APP-C99 triggers the pathogenesis of Alzheimer disease. “In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate. . .C99 that is then cleaved. . .to generate the beta-amyloid (Aß) found in senile plaques. . .Whereas C99 is normally processed rapidly, it accumulates in cells from AD patient and animal models. . .aberrant APP processing in AD results in the accumulation of . . .C99, which is the fundamental effector of the pathogenesis of AD ([00322]).
Thus, it would reasonably be expected that prior to treatment, a subject with AD (i.e., the subject treated in instant claim 14), would have a higher ratio of C99 to total Aß, than a subject without AD, since accumulation of C99 is a hallmark of AD. See MPEP 2112.02.
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 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.
(Modified) Claims 14-16 are rejected under 35 U.S.C. 103 as being unpatentable over US 6,043,224 to Lee (published 2000, PTO-892).
Lee teaches a method of modulating expression, production, or formation of amyloid precursor protein (APP) in a subject comprising administering to the subject an effective amount of a substance that is a ligand, an agonist, or an antagonist of a receptor that is coupled to cellular levels of cAMP (claim 1), wherein isoproterenol is taught as such a substance (claims 1, 3).
Lee teaches its methods as alleviating, treating, or preventing Alzheimer’s disease (abstract, Col. 5, lines 10-16).
Amyloid plaques in Alzheimer’s disease (AD) accumulate near dystrophic neurons and reactive astrocytes. The activation of neurotransmitter receptors, which are coupled to phosphatidylinositol hydrolysis or to protein kinase C, can promote amyloid precursor protein (APP) metabolism and decrease amyloid formation. Increased secretion of APPs disrupt formation of amyloidogenic Abeta peptides (Col. 1, lines 49-Col. 2, line 17; Col. 5, lines 19-Col. 6, line 10).
Lee teaches isoproterenol as stimulating APP mRNA production (abstract; Col. 6, lines 15-21, Fig. 1C; Col. 7, line 10-24; Col. 12, lines 30-44; Col. 22, line 55-Col. 23, line 35).
Lee teaches that the specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific compound employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coinciding with the specific compound employed; and like factors well known in the medical arts. Lee specifically teaches a dosage amount of 0.05-25 mg/kg (Col. 15, line 58-Col. 16, line 36).
While Lee teaches a method of stimulating APP production in a subject by administering isoproterenol, it differs from that of the instant claim 14 in that it does not explicitly state a method of treating Alzheimer’s disease in a subject by administering isoproterenol.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select Alzheimer’s disease as the disease treated by the administration of isoproterenol, to arrive at instant claim 14. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because,
-Lee teaches its methods as alleviating, treating, or preventing Alzheimer’s disease by administering compounds that increase APP production to decrease amyloid formation, and thus amyloid plaques,
-Lee teaches isoproterenol as stimulating APP production.
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection to predictably arrive at a method of treating Alzheimer’s disease by increasing APP and thus, decreasing amyloid plaque formations.
The wherein clause in the last three lines of claim 14 does not recite any active steps in which the C99 and amyloid beta levels of subjects with and without AD, are measured and determined. The wherein clause recites a property of a subject with Alzheimer’s Disease in comparison to that of a subject without Alzheimer’s Disease.
As evidenced by the instant specification, AD subjects have a higher ratio of C99 to beta-amyloid than subjects without AD. Example 1, beginning on pg. 100 of the instant specification teaches that accumulation of APP-C99 triggers the pathogenesis of Alzheimer disease. “In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate. . .C99 that is then cleaved. . .to generate the beta-amyloid (AB) found in senile plaques. . .Whereas C99 is normally processed rapidly, it accumulates in cells from AD patient and animal models. . .aberrant APP processing in AD results in the accumulation of . . .C99, which is the fundamental effector of the pathogenesis of AD ([00322]).
Thus, it would reasonably be expected that prior to treatment, a subject with AD (i.e., the subject treated in instant claim 14), would have a higher ratio of C99 to total beta-amyloid, than a subject without AD, since accumulation of C99 is a hallmark of AD. See MPEP 2112.02.
Regarding claims 15 and 16, Lee teaches isoproterenol.
(Modified) Claims 14-15 and 17 is rejected under 35 U.S.C. 103 as being unpatentable over US 2008/0014152 to Di Mauro (published 2008, PTO-892).
Di Mauro teaches a method of treating a neurodegenerative disease by administering an effective amount of clenbuterol (pg. 4, claims 1-4; pg. 5, claims 21-24).
Di Mauro teaches its methods for the treatment of Alzheimer’s disease (AD) ([0003]; [0005]; [0013]; [0037]).
Di Mauro teaches clenbuterol as a NGF inducer, wherein NGF within an AD brain is very important as it is a neurotrophic factor essential to the development of cholinergic neurons in the basal forebrain, which play an important role in learning and memory process. As such it enhances learning and memory processes in AD patients ([0003], [0005], [0008]).
While Di Maura teaches a method of treating a neurodegenerative disease by administering an effective amount of clenbuterol, it differs from that of the instantly claimed invention in that it does not explicitly teach a method of treating Alzheimer’s disease by administering clenbuterol to a subject.
It would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the instantly claimed invention, to select the methods of Di Mauro to treat patients with Alzheimer’s disease, to arrive at instant claim 14. One of ordinary skill in the art would have been motivated to make such a selection, with a reasonable expectation of success, because:
-Di Mauro teaches a method of treating neurodegenerative disease by administering the NGF inducing agent, clenbuterol,
-Di Mauro teaches NGF within an AD brain as very important because it is a neurotrophic factor essential to the development of cholinergic neurons in the basal forebrain, which enhance learning and memory processes in AD patients, and
-Di Mauro teaches its methods for the treatment of Alzheimer’s disease.
As such, an artisan having ordinary skill in the art would have been motivated to make such a selection, to predictably arrive at a method of treating Alzheimer’s disease that enhances learning and memory processes.
The wherein clause in the last three lines of claim 14 does not recite any active steps in which the C99 and amyloid beta levels of subjects with and without AD, are measured and determined. The wherein clause recites a property of a subject with Alzheimer’s Disease in comparison to a subject without Alzheimer’s Disease.
As evidenced by the instant specification, AD subjects have a higher ratio of C99 to beta-amyloid than subjects without AD. Example 1, beginning on pg. 100 of the instant specification teaches that accumulation of APP-C99 triggers the pathogenesis of Alzheimer disease. “In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate. . .C99 that is then cleaved. . .to generate the beta-amyloid (AB) found in senile plaques. . .Whereas C99 is normally processed rapidly, it accumulates in cells from AD patient and animal models. . .aberrant APP processing in AD results in the accumulation of . . .C99, which is the fundamental effector of the pathogenesis of AD ([00322]).
Thus, it would reasonably be expected that prior to treatment, a subject with AD (i.e., the subject treated in instant claim 14), would have a higher ratio of C99 to total beta-amyloid, than that of a subject without AD, since accumulation of C99 is a hallmark of AD. See MPEP 2112.02.
Regarding claims 15 and 17, Di Mauro teaches clenbuterol.
Response to Arguments
On pgs. 8 Remarks, Applicant argues that Lee and DiMauro fail to identify a patient population with AD based on a ratio of C99 to total Aß.
This argument has been fully considered, but is not found persuasive.
As discussed in the above rejection:
The wherein clause in the last three lines of claim 14 does not recite any active steps in which the C99 and amyloid beta (Aß) levels of subjects with and without AD, are measured and determined. The wherein clause recites a property of a subject with Alzheimer’s Disease in comparison to a subject without Alzheimer’s Disease.
As evidenced by the instant specification, AD subjects have a higher ratio of C99 to beta-amyloid than subjects without AD. Example 1, beginning on pg. 100 of the instant specification teaches that accumulation of APP-C99 triggers the pathogenesis of Alzheimer disease. “In the amyloidogenic pathway associated with Alzheimer disease (AD), the amyloid precursor protein (APP) is cleaved by beta-secretase to generate. . .C99 that is then cleaved. . .to generate the beta-amyloid (Aß) found in senile plaques. . .Whereas C99 is normally processed rapidly, it accumulates in cells from AD patient and animal models. . .aberrant APP processing in AD results in the accumulation of . . .C99, which is the fundamental effector of the pathogenesis of AD ([00322]).
Thus, it would reasonably be expected that prior to treatment, a subject with AD (i.e., the subject treated in instant claim 14), would have a higher ratio of C99 to total Aß, than that of a subject without AD, since accumulation of C99 is a hallmark of AD. See MPEP 2112.02.
Further regarding Lee, on pg. 8, Remarks, Applicant argues that Lee teaches isoproterenol to increase APP production, but that the present disclosure teaches using isoproterenol to increase gamma-secretase activity to cleave APP for degradation and to process APP-C99 away from the mitochondrial associated membrane (MAM), and that Lee appears to teach the opposite effect.
This argument has been fully considered, but is not found persuasive. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965). Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See MPEP 716.01(c). Applicant has provided no evidence that the methods of Lee which administer the same drug, isoproterenol, to the same patient population (patients with Alzheimer’s disease), in an amount effective to treat Alzheimer’ disease, would have not have the same effect. Moreover, it is respectfully pointed out that the wherein clause is directed to the state of an Alzheimer’s patient prior to treatment.
Further, it is noted that Lee was effectively filed in 1996 and published in 2000. As such, it is reasonable to assume that medical advances have been made in elucidating the in-vivo, biochemical pathways involved in Alzheimer’s disease. Lee does not teach C99, but similar to the instant claims, recites a method of treating Alzheimer’s disease by administering the same drug, isoproterenol, to the same patient population (patients with Alzheimer’s disease), in an amount effective to treat Alzheimer’ disease, wherein amyloid plaque formation is decreased (See Col. 4, lines 66-67; Col. 5, lines 10-16; Col. 12, lines 30-44; Col. 22, lines 30-54; Col. 23, lines 9-17 of Lee; and [00476]; [00760]; [00900]; [00958] of the instant specification).
Moreover, “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. . .’The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious,’” see MPEP 2145(II),
For these reasons, Applicant’s arguments are not persuasive to overcome the prior art rejections.
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 LAUREN WELLS whose telephone number is (571)272-7316. The examiner can normally be reached M-F 7:00-4:30.
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/LAUREN WELLS/Examiner, Art Unit 1622