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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 18, 2026 has been entered.
Claims 1, 5-12 and 14-17 are pending in this application and are examined on the merits in this office action.
Withdrawn Rejection
Rejection of claims 1, 5-6 and 8-12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is hereby withdrawn in view of Applicant’s amendment to the claims.
Rejections of claims 6, 8-10 and 12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are hereby withdrawn in view of Applicant’s amendment to the claims. However, Applicant has not amended claim 15 to overcome the rejection under 35 U.S.C. 112(b).
Maintained Rejection
35 U.S.C. 112(b)
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 15 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 15 recites parenthetical expression “(any form of tobacco)”. The metes and bounds of the claim 15 is rendered vague and indefinite by the parenthetical recitation of “(any form of tobacco)” because it is unclear as to whether the limitation is part of the instantly claimed subject matter. See MPEP 2173.05(d).
Response to Applicant’s Arguments
Applicant argues that, “Applicant has amended claim 15 to delete the parenthetical expression. Applicant respectfully submits that this amendment renders the claim definite.”
Applicant’s arguments have been fully considered but are not found persuasive. Applicant has not amended claim 15 to delete the parenthetical expression. Therefore, the rejection is maintained.
35 U.S.C. 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, 5-12, 14 and 16-17 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Groeneveld et al (Journal of Diabetes Investigation, 2016, 7: 5-16, cited in the previous office action) in view of Zimmer et al (US 2019/0142905, filed with IDS).
Groeneveld et al teach that patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes (see abstract, lines 1-3), meeting the limitation of instant claims 1, 5-7 and 9, in part. Groeneveld et al teach that incretin-based therapies might have direct or indirect beneficial effects on the brain…the potential of incretin-based therapies in relation to dementia, in particular Alzheimer’s disease, and stroke in patients with type 2 diabetes (see abstract, lines 7-10). Groeneveld et al teach:
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(p. 6, left column, top). Groeneveld et al teach that cognitive impairment and dementia are increasingly recognized as important complications of type 2 diabetes mellitus. For instance, patients with type 2 diabetes mellitus perform slightly worse on a range of cognitive tasks, compared with patients without type2 diabetes mellitus. The rate of cognitive decline in patients with type 2 diabetes mellitus can be up to twofold faster compared with normal aging. Patients with type 2 diabetes mellitus have an increased risk for MCI, compared with patients without type 2 diabetes mellitus (see p. 7, right column, bottom). Groeneveld et al teach that glycemic control is an obvious candidate as to what causes accelerated cognitive decline and increased dementia risk in patients with type 2 diabetes mellitus (see p. 8, left column, lines 5-8). As evidenced by instant specification, Applicant defines substantive cognitive decline or SCD as “a significant decrease in a subject’s score in a standardized cognitive assessment, such as MoCA or DSST of 1.5 standard deviations or greater” (see paragraph [0018]). Therefore, Groeneveld et al teach the same patient population (i.e., patients with type 2 diabetes mellitus perform worse on a range of cognitive tasks…the rate of cognitive decline in patients with type 2 diabetes mellitus can be up to twofold faster…). Groeneveld et al teach the following:
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(see p. 11, right column, “CONCLUSION”).
In regards to instant claims 6-9, the claims recite an end result. With respect to “wherein the method results in a reduction in the risk of the patient experiencing SCD (claim 6); wherein the method results in a reduction in the risk of the patient experiencing SCD (claim 7); wherein the patient’s risk of cognitive decline is reduced by about 14% (claim 8); wherein the patient’s risk of the occurrence of a composite of the following outcome is reduced: SCD, stroke, transient ischemic attack or death (claim 9)” according to MPEP 2111.04: "Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) “adapted to” or “adapted for” clauses;
(B) “wherein” clauses; and
(C) “whereby” clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a “whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention.” Id. However, the court noted (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Id. <”. In the instant case, it is not deemed that the “wherein” clause limits the claim to particular structural features. The wherein clause only recite the end result.
The difference between the reference and the instant claims is that the reference does not teach the therapeutically effective amounts of dulaglutide administered.
However, Zimmer et al teach a method of treating, for example, a cognitive disease or disorder, by administering a compound comprising GLP-1 analog having at least one amino acid of the compound substituted with a residue selected from an aminourea, an aminothiourea, and an aminoguanidine, wherein the disease or disorder is selected from…neurodegenerative of cognitive disease or disorder, a heart disease…cardiovascular disease…strokes, or a combination thereof (see paragraph [0011], for example). Zimmer et al teach that the GLP-1 analog is selected from the group consisting of lixisenatide, exendatide, semaglutide, liraglutide, albiglutide, dulaglutide (see for example, paragraph [0012] and claim 2). Zimmer et al further teach that the cognitive disease or disorder includes dementia (see for example, paragraph [0014] and claim 4). Zimmer et al teach that dulaglutide is a GLP-1 agonist for the treatment of type 2 diabetes that can be used once weekly. GLP-1 hormone that is involved in the normalization of level of glucose in blood (glycemia) (see paragraph [0335]). Zimmer et al teach treating a disease or disorder or ameliorating the effects of the same comprising the steps of administering to an individual in need thereof, a composition comprising an effective amount of a compound or salt form thereof…and a pharmaceutically acceptable carrier or excipient, wherein the composition is effective for treating, preventing or ameliorating the effects of the disease or disorder (see for example, paragraph [0065]). Zimmer et al further teach that the disease or disorder is selected from the group consisting of diabetes (such as diabetes mellitus type 1 or diabetes mellitus type 2), a neurodegenerative disease or disorder (such as peripheral neuropathy, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic sclerosis, multiple sclerosis…), or a combination thereof (see paragraph [0066], and claims 1-2, for example). Furthermore, Zimmer et al teach that a preferred dose of the active compound is in the range from about 10 ng/kg to 300 mg/kg, preferably 0.1 to 100 mg/kg per day…0.5 to 25 mg/kg body weight…less than 1 mg, 1 mg to 3000 mg, preferably 5 to 500 mg of active ingredient per unit dosage form. An oral dosage of about 25-250 mg…(see paragraph [0292]). As an example, Zimmer et al teach that Exenatide administration at the same rate through 2.25 years of continued use (see for example, paragraph [0322]).
Zimmer et al and the do not explicitly teach the effective amount of about 1.5 mg, about 3.0 mg and about 4.5 mg.
However, Zimmer et al teach that a preferred dose of the active compound is in the range from about 10 ng/kg to 300 mg/kg, preferably 0.1 to 100 mg/kg per day…0.5 to 25 mg/kg body weight…less than 1 mg, 1 mg to 3000 mg, preferably 5 to 500 mg of active ingredient per unit dosage form. An oral dosage of about 25-250 mg…(see paragraph [0292]). Zimmer et al teach an effective dose amount that encompasses instant 1.5 mg, 3.0 mg and 4.5 mg.
Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Groeneveld et al and Zimmer et al, because both references teach a method of treating cognitive decline in a patient with type 2 diabetes mellitus with incretin-based therapies (e.g., GLP-1 agonist such as exendin-4, exenatide, liraglutide, lixisenatide and dulaglutide). One of ordinary skill in the art would be motivated to combine with a reasonable expectation of success, since Groeneveld et al teach that incretin-based therapies hold a promise in the treatment of dementia, in particular AD and stroke, and Zimmer et al teach the GLP-1 analogs in methods of treatment of cognitive decline. One of ordinary skilled in the art would be motivated to optimize the effective dosage amount with a reasonable expectation of success, since Zimmer et al teach an dosage amount that encompasses instant effective dosage (1.5 mg, 3.0 mg and 4.5 mg). The MPEP states the following: “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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). One of ordinary skill in the art would be motivated to optimize with a reasonable expectation of success, since “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”
Regarding the limitation to the amount of the composition administered to the patient, the result-effective adjustment in conventional working parameters (e.g., determining an appropriate amount of the active agent within the composition, or the effective amount to administered to the patient in need thereof) is deemed merely a matter of judicious selection and routine optimization which is well within the purview of the skilled artisan, which is dependent on the crop and amount of insect control that is needed.
From the teachings of the references, it is apparent that one of the ordinary skills in the art would have had a reasonable expectation of success in producing the claimed invention.
Thus, the invention as a whole is prima facie obvious over the reference, especially in the absence of evidence to the contrary.
Response to Applicant’s Arguments
Applicant argues that, “Zimmer’s disclosure of dose ranges cited by the Office, however, does not relate to dulaglutide. Rather than teaching use of dulaglutide itself, Zimmer instead identifies dulaglutide as an example of a “parent” or “parental” molecule whose properties may be improved through use of purportedly novel modifications.” Applicant further argues that “…the cited portions of Groeneveld and Zimmer fail to disclose a patient having type 2 diabetes mellitus (T2DM) and either: multiple cardiovascular risk factors without established cardiovascular disease; or established cardiovascular disease” as recited in claims 1 and 5.” Applicant argues that “…the field of treating cognitive disorders is well-recognized as highly unpredictable…In the enablement analysis, the Examiner stated that “the predictability in the art is low,” (OA at 7) and acknowledged that “there are presently no treatments that can stop or reverse the inexorable neurodegenerative process” (OA at 10)…”
Applicant’s arguments have been fully considered but are not found persuasive. Instant rejection is a 35 U.S.C. 103 rejection (obviousness). Groeneveld et al explicitly teach the nexus between type 2 diabetes mellitus patients and cognitive disorders. For example, as indicated in the rejection above, Groeneveld et al teach that patients with type 2 diabetes mellitus are at risk for accelerated cognitive decline and dementia. Furthermore, their risk of stroke is increased and their outcome after stroke is worse than in those without diabetes. Groeneveld et al teach that incretin-based therapies might have direct or indirect beneficial effects on the brain…the potential of incretin-based therapies in relation to dementia, in particular Alzheimer’s disease, and stroke in patients with type 2 diabetes. Groeneveld et al teach that cognitive impairment and dementia are increasingly recognized as important complications of type 2 diabetes mellitus. For instance, patients with type 2 diabetes mellitus perform slightly worse on a range of cognitive tasks, compared with patients without type 2 diabetes mellitus. Zimmer et al teach a method of treating, for example, a cognitive disease or disorder, by administering a compound comprising GLP-1 analog, wherein the disease or disorder is selected from…neurodegenerative of cognitive disease or disorder, a heart disease…cardiovascular disease…strokes, or a combination thereof. Zimmer et al teach that the GLP-1 analog is selected from the group consisting of lixisenatide, exendatide, semaglutide, liraglutide, albiglutide, dulaglutide. Zimmer et al further teach that the cognitive disease or disorder includes dementia. Zimmer et al teach that dulaglutide is a GLP-1 agonist for the treatment of type 2 diabetes that can be used once weekly. GLP-1 hormone that is involved in the normalization of level of glucose in blood (glycemia), and teach treating a disease or disorder or ameliorating the effects of the same comprising the steps of administering to an individual in need thereof, a composition comprising an effective amount of a compound or salt form thereof…and a pharmaceutically acceptable carrier or excipient, wherein the composition is effective for treating, preventing or ameliorating the effects of the disease or disorder, selected from the group consisting of diabetes (such as diabetes mellitus type 1 or diabetes mellitus type 2), a neurodegenerative disease or disorder (such as peripheral neuropathy, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic sclerosis, multiple sclerosis…), or a combination thereof. Furthermore, Zimmer et al teach that a preferred dose of the active compound is in the range from about 10 ng/kg to 300 mg/kg, preferably 0.1 to 100 mg/kg per day…0.5 to 25 mg/kg body weight…less than 1 mg, 1 mg to 3000 mg, preferably 5 to 500 mg of active ingredient per unit dosage form. An oral dosage of about 25-250 mg. As an example, Zimmer et al teach that Exenatide administration at the same rate through 2.25 years of continued use. Although Zimmer et al do not explicitly teach the dosage of dulaglutide, one of ordinary skill in the art can once envisage similar dosage of dulaglutide from the Exenatide dosage range. The MPEP states the following: When the compound is not specifically named, but instead it is necessary to select potions of teachings within a reference and combine them, e.g., select various substituents from a list of alternatives given for placement at specific sites on a generic chemical formula to arrive at a specific composition, anticipation can only be found if the classes of substituents are sufficiently limited or well delineated. Ex parte A, 17 USPQ2d1716 (Bd. Pat. App. & Inter. 1990). If one of ordinary skill in the art is able to "at once envisage" the specific compound within the generic chemical formula, the compound is anticipated (See MPEP 2105). Zimmer et al teach limited number of GLP-1 analogs for treating, preventing or ameliorating the effects of the disease or disorder, selected from the group consisting of diabetes (such as diabetes mellitus type 1 or diabetes mellitus type 2), a neurodegenerative disease or disorder (such as peripheral neuropathy, Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, amyotrophic sclerosis, multiple sclerosis…), or a combination thereof.
In regards to Applicant’s argument “the field of treating cognitive disorders is well-recognized as highly unpredictable…In the enablement analysis, the Examiner stated that “the predictability in the art is low,” (OA at 7) and acknowledged that “there are presently no treatments that can stop or reverse the inexorable neurodegenerative process (OA at 10)”, in the enablement rejection, the Examiner indicated “while being enabling for delaying substantive cognitive decline (SCD), does not reasonably provide enablement for preventing substantive cognitive decline (SCD)”. Thus, the enablement rejection was based on the recitation of “preventing substantive cognitive decline (SCD)” which the Applicant has amended the claim to delete the term “preventing”. Thus, the “unpredictability” argument is moot.
Therefore, the combined art is prima facie obvious over instant claims 1, 5-12, 14 and 16-17. The rejection is deemed to be proper and is maintained herein.
CONCLUSION
No claim is allowed.
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/JULIE HA/Primary Examiner, Art Unit 1654
7/27/2026
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