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 .
Election/Restrictions
Applicant’s election without traverse of exenatide as the species of GLP-1RAs and gene expression of C1qa in the reply filed on July 1st, 2026 is acknowledged.
Applicant states that claim 12 reads on the elected species of exenatide. However, claim 12 is directed towards derivatives of exenatide, not exenatide itself, and is therefore not examined.
Claims 10-12, 14, and 16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 1st, 2026.
Priority
The priority date of the application is the filing date, December 22nd, 2023.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) filed December 6th, 2024 is considered by the examiner.
Claims Status
The claims listing filed on December 22nd, 2023 is pending. Claims 10-12, 14, and 16 are withdrawn from further consideration for the reasons set forth in the restriction requirement, 37 CFR 1.142(b). Claims 1-9, 13, and 15 are being examined on the merits in this office action.
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, 8, 13 and 15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 18257745 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims anticipate each other.
Note: Examiner acknowledges the terminal disclaimer filed under Application No. 18257745 for the provisional rejection with the present application. However, the terminal disclaimer has to be filed under the present application to take effect as it has a later priority date.
Regarding claim 1, ‘745 claims:
A method of treating a subject for aging-associated brain functional impairment, the method comprising administering to the subject an effective amount of a glucagon-like peptide-1 receptor (GLP-1R) agonist whereby the aging-associated brain functional impairment is treated, wherein the aging-associated brain functional impairment comprises any of aging-associated measurable structural, functional, or molecular change of the brain; wherein the aging-associated measurable molecular change is a change in gene expression, transcription of Deoxyribonucleic acid (DNA), translation of Ribonucleic acid (RNA), location of DNA, RNA, or protein in brain cells or tissue; or a secretion or release of proteins, DNA, RNA, mitochondria, cellular components, or mitochondrial components into blood fluids; wherein the efficacy of the treatment is assessed by the reverse of aging-associated brain molecular changes, wherein the molecular changes are assessed by measuring changes in gene expression in (i) immune response-related genes selected from the group consisting of C1qa, C1qb, Clqc, C4b, B2m, Tap2, H2-D1, and H2-K1; (ii) synaptic modification-related genes selected from the group consisting of Sparcll, Gpc6, Tgfb2, Megfl0, Mertk, and Chrdll; (iii) homeostatic function-related genes selected from the group consisting of Kcnil0, Kcnn2, Slcla2, Slcla3, Slc6al, Slc6a9, Slc6all, Slc7a10, Slc7all, Slcl6al, Srebfl, Gial, Gib6, Itpr2, Grm3, Gria2, Gabbrl, and Gabbr2; homeostatic-related genes in MG cells selected from the group consisting of Csf2r, and P2ry13; immune activation-related genes in MG cells selected from the group consisting of Appe, Ccl3, Ccl4, 30 Cd52, Cst7, Fabp5, Tyrobp, Cd14, Cd33, Ifngrl, Ly86, and Map4k4; immune response inhibitory genes in MG cells selected from the group consisting of Cd300a, Ill Ora, and Ill Orb; calcium signaling-related genes in SMCs selected from the group consisting of Camk2a, Stiml, Gsn, Atp2a2, Inp4b, Mcurl, S1OOa6, and Tspo;SMC contraction-related genes selected from the group consisting of Mylk, Itgal, Mghll, and Sorbsl; and (iv) cell adhesion and ECM remodeling genes in SMCs selected from the group consisting of Colla2, Lamb1, Itga7, Jam3, Lamb2, Itgbl, and Bsg. [claim 1]
‘745 further claims the method,
“wherein the GLP-1R agonist is exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide, taspoglutide, PF-06882961, OWL- 833, or TTP-273” [claim 2].
Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount of glucagon-like peptide 1 receptor agonist (GLP-1RA), wherein the GLP-1RA is exenatide.
Regarding claim 2, ‘745 further claims the method, wherein the subject is a mammal [claims 1 and 4]. Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the subject is a mammal.
Regarding claim 3, ‘745 further claims the method, wherein the subject is a primate [claims 1 and 4-5]. Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the subject is a primate.
Regarding claim 4, ‘745 further claims the method, wherein the subject is a human [claims 1 and 4-6]. Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the subject is a human.
Regarding claim 5, ‘745 further claims the method, wherein the subject is 50 years of age or older or a mouse of 16 months or older [claims 1 and 7]. Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the subject is 50 years or older.
Regarding claim 8, ‘745 further claims the method, wherein the aging-associated brain function impairment comprises cognitive impairment [claims 1 and 7]. Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the aging-associated function impairment is cognitive impairment.
Regarding claim 13, ‘745 claims:
“A method of treating a subject for aging-associated brain functional impairment, the method comprising administering to the subject an effective amount of a glucagon-like peptide-1 receptor (GLP-1R) agonist whereby the aging-associated brain functional impairment is treated, wherein the aging-associated brain functional impairment comprises any of aging-associated measurable structural, functional, or molecular change of the brain; wherein the aging-associated measurable molecular change is a change in gene expression…” [claim 1].
Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the aging-associated functional change is a change in an expression of at least one gene in the subject.
Regarding claim 15, ‘745 claims:
A method of treating a subject for aging-associated brain functional impairment, the method comprising administering to the subject an effective amount of a glucagon-like peptide-1 receptor (GLP-1R) agonist whereby the aging-associated brain functional impairment is treated, wherein the aging-associated brain functional impairment comprises any of aging-associated measurable structural, functional, or molecular change of the brain; wherein the aging-associated measurable molecular change is a change in gene expression, transcription of Deoxyribonucleic acid (DNA), translation of Ribonucleic acid (RNA), location of DNA, RNA, or protein in brain cells or tissue; or a secretion or release of proteins, DNA, RNA, mitochondria, cellular components, or mitochondrial components into blood fluids; wherein the efficacy of the treatment is assessed by the reverse of aging-associated brain molecular changes, wherein the molecular changes are assessed by measuring changes in gene expression in (i) immune response-related genes selected from the group consisting of C1qa, C1qb, Clqc, C4b, B2m, Tap2, H2-D1, and H2-K1…” [claim 1].
Therefore, ‘745 anticipates a method for decreasing an aging-associated functional change in a subject comprising administering to the subject an effective amount exenatide, wherein the aging-associated functional change is a change in an expression of at least one gene in the subject, wherein the at least one gene is C1qa.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 6 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-9 of copending Application No. 1825745, as applied to claims 1-5, 8, 13 and 15, in view of Wu et al. (Wu, L., Zhou, M., Li, T., Dong, N., Yi, L., Zhang, Q., & Mi, M. (2022). GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway. Biochimica et biophysica acta. Molecular cell research, 1869(9), 119300.).
Regarding claim 6, '745 does not claim using exenatide in a method for decreasing an aging-associated functional change, wherein the aging-associated functional change is a reduction of muscle endurance.
Wu et al. demonstrate that GLP-1 enhances physical endurance capacity by inducing skeletal muscle remodeling, which may be mediated by GLP-1R/AMPK signaling pathway [Introduction pgh 4 line 7] When they assessed whether GLP-1 overexpression would affect muscle endurance, using an exhaustive swimming test, they found that the mice showed increased endurance capacity [Section 3.2 pg 1 line 35].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to claim a method of decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a glucagon-like peptide 1 receptor agonist (GLP-1RA), such as exenatide, wherein the aging-associated functional change is a reduction of muscle strength, balance, muscle endurance, or any combination thereof because Wu et al. demonstrate that GLP-1 increases muscle endurance.
Regarding claim 9, '745 does not claim using exenatide in a method for decreasing an aging-associated functional change, wherein the aging-associated functional change is a measurable change in skeletal muscle activity. However, Wu et al. states,
“Our results showed that over expression of GLP-1 in skeletal muscle enhances endurance capacity. Endurance exercise has been shown to remodel the skeletal muscle, to keep up with the increase in energy demands, thereby improving endurance capacity [25,26]. Skeletal muscle remodeling, such as muscle fiber type switch, muscle mitochondrial content and mass, and energy substrate utilization, determines exercise endurance capacity in turn” [Discussion pgh 3 line 5].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to claim a method of decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a glucagon-like peptide 1 receptor agonist (GLP-1RA), such as exenatide, wherein the aging-associated functional change is a measurable change in colon activity, adipose tissue amount, circulating white blood cell amount, spleen activity, lung airflow, skeletal muscle activity, heart activity, liver activity, kidney activity, or any combination thereof. This is because Wu et al. teach that GLP-1 agonists, such as the exenatide claimed by ‘745., would result in a measurable change in skeletal muscle activity because overexpression of GLP-1 results in skeletal muscle remodeling.
This is a provisional nonstatutory double patenting rejection.
Claims 7 and 9 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of copending Application No. 18257745, as applied to claims 1-5, 8, 13 and 15, in view of Ding et al (Ding, W., Chang, W. G., Guo, X. C., Liu, Y., Xiao, D. D., Ding, D., Wang, J. X., & Zhang, X. J. (2019). Exenatide Protects Against Cardiac Dysfunction by Attenuating Oxidative Stress in the Diabetic Mouse Heart. Frontiers in endocrinology, 10, 202.).
Regarding claim 7, ‘745 does not claim using exenatide in a method for decreasing an aging-associated functional change, wherein the aging-associated functional change is a decrease in heart ejection fraction.
Ding et al. teaches that the ejection fraction percentages were significantly decreased in type 2 (T2DM) and type 1 diabetes mice (T1DM), compared to the control (CON) mice, but treatment with exenatide restored the heart ejection fraction percentages of type 2 diabetes mice to that of the control group [pg 4 pgh 1 line 12]. Therefore, prior to the effective filing date, it would have been obvious to claim a method of decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a glucagon-like peptide 1 receptor agonist (GLP-1RA), such as exenatide, wherein the aging-associated functional change is a decrease in heart ejection fraction.
Regarding claim 9, ‘745 does not claim using exenatide in a method for decreasing an aging-associated functional change, wherein the aging-associated functional change is a measurable change in heart activity. Ding et al. teaches that the EF% (ejection fraction), LVSD (left ventricular end-systolic diameter), and LVDD (left ventricular end-diastolic diameter) were used to determine systolic function, and FS% (fractional shortening) and E/A (ratio of the early (E) to late (A) ventricular filling velocities) were used to determine diastolic function [pg 4 pgh 1 line 1]. Systolic and diastolic dysfunction developed in T2DM and T1DM animals in comparison to CON mice, but exenatide treatment of T2DM animals attenuated this dysfunction. Therefore, it was obvious to claim a method of decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a glucagon-like peptide 1 receptor agonist (GLP-1RA), such as exenatide, wherein the aging-associated functional change is a measurable change in colon activity, adipose tissue amount, circulating white blood cell amount, spleen activity, lung airflow, skeletal muscle activity, heart activity, liver activity, kidney activity, or any combination thereof prior to the effective filing date.
This is a provisional nonstatutory double patenting rejection.
Claim Rejections - 35 USC § 112
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, 13, and 15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for decreasing a reduction of muscle strength, balance, and muscle endurance, decrease in heart ejection fraction, and cognitive impairment does not reasonably provide enablement for decreasing all aging-associated functional changes. 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.
The breadth of the claim encompasses using the GLP-1R agonists to treat any aging-associated functional change. The applicant does not specify what an aging-associated functional change is. The specification states that during “the process of aging, functional changes may occur in individual or multiple organs throughout the body of a subject” [pg 8 line 23]. The invention’s nature is therapeutic, comprising administering an effective amount of a GLP-1R agonist. The genus “GLP-1 agonist” is not limited to long-acting peptide agonists but also includes peptides that are not modified for extended use and small molecules. However, the state of the prior art does not support that all GLP-1 agonists can treat all types aging-associated functional change (Remy, M. (2023). Does estrogen replacement therapy stop menopause? | HerKare. In HerKare. https://herkare.com/blog/does-estrogen-replacement-therapy-stop-menopause)
Remy shares that estrogen replacement therapy alleviates menopause symptoms, but does not actually stop or delay menopause [pgh 1]. Menopause is a natural process that women go through, not a condition that you can “cure” [pgh 3]. Thus, Remy sets forth that there is no receptor-targeting therapy that can stop or delay menopause. One of ordinary skill in the art would recognize that aging-associated functional changes caused by genetic, epigenetic, and lifestyle factors cannot be decreased by a GLP-1R agonist.
The inventors provide direction by demonstrating the effect of 6-month exenatide treatment on body weight, food intake, exercise capacities, spatial reference memory, and body-wide aging associated transcriptomic changes on aged mice [pg 25 line 15 to pg 27 line 11 and Fig 2-10]. The inventors provide adequate support in the specification for a GLP-IRA’s ability to impact aging-associated functional change represented by exercise capacities and spatial reference memory. However, this does not extend the predictability that a GLP-1RA would be able to decrease all aging-associated functional changes.
Moreover, in order to practice the full scope of the claimed invention, the applicant would be burdened with discovering which additional aging-associated functional changes can be treated with GLP-1 agonists. This requirement to discover, test, and validate constitutes undue experimentation. Thus, while the applicant is enabled for the scope of decreasing a reduction of muscle strength, balance, and muscle endurance, decrease in heart ejection fraction, and cognitive impairment, the inventor is not enabled for decreasing the complete genus of aging-associated functional changes.
Claims 2-5 do not further limit the genus of aging-associated functional changes decreased in base claim 1, and are therefore rejected for not being supported by specification under the enablement requirement
Claim 13 limits the genus of aging-associated functional changes decreased in base claim 1 to being characterized by a change in an expression of at least one gene. However, the inventor is not enabled for the complete genus of decreasing aging-associated functional changes characterized by a change in an expression of at least one gene. (Sárvári, M., Hrabovszky, E., Kalló, I., Solymosi, N., Likó, I., Berchtold, N., Cotman, C., & Liposits, Z. (2012). Menopause leads to elevated expression of macrophage-associated genes in the aging frontal cortex: rat and human studies identify strikingly similar changes. Journal of neuroinflammation, 9, 264.)
Sarvari et al. explore the impact of menopause on the expression of genes related to the innate immune system in the rat and human cerebral cortex using ovariectomized rat models [pg 2 pgh 2 line 1 and Methods]. Real-time PCR demonstrated age- and ovariectomy-related increase in the expression of Cd32, Msr2, C1qb, C3, and decrease of Cd93 and Cd36 [Fig 2]. Therefore, not all changes in gene expression that are age-related can be explained by functional changes enabled to be decreased by GLP-1RAs, like functional changes due to menopause.
Regarding claim 15, the gene C1qb’s expression increases during menopause [Fig 2]. However, menopause in a natural process, undelayable by medicine. Therefore, the applicant is not enabled for the complete scope of decreasing aging-associated functional change characterized by a change in an expression of at least gene, such as C1qb.
Claim 8 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 8 recites the limitation "the aging-associated function impairment" in line 1. This phrase is not previously used in a base claim. There is insufficient antecedent basis for this limitation in the claim. The applicant may remedy this by replacing the phrase with “aging-associated functional change.”
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.
Claims 1-5, 8, 13 and 15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ko et al (WO2022127868A1; published June 2022).
The applied reference has common assignees and inventors with the instant application. Based upon the publication date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(1) and the exceptions under 35 U.S.C. 102(b)(1) do not apply.
The following rejection is made based on applicant’s election of exenatide as the species of GLP-1RAs and gene expression of C1qa in the reply filed on July 1st, 2026.
Regarding claim 1, Ko et al. claims a method of treating a subject for aging-associated brain functional impairment, the method comprising administering to the subject an effective amount of a GLP-1R agonist, wherein the GLP-1R agonist is exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide, taspoglutide, PF-06882961, OWL-833, or TTP-273, or any other molecule that activates GLP-1R [claims 1 and 2].
Therefore, Ko et al. anticipates a method for decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a glucagon-like peptide 1 receptor agonist (GLP-1RA); wherein the GLP-1RA is exenatide.
Regarding claim 2, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the subject is a mammal [claim 4].
Regarding claim 3, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the subject is a mammal, and wherein the mammal is a primate [claim 5].
Regarding claim 4, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the subject is a human [claim 6].
Regarding claim 5, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the subject is 50 years or older [claim 7].
Regarding claim 6, Ko et al. does not teach using a GLP-1R agonist to decrease a reduction in muscle endurance. However, the limitation “wherein the aging-associated functional change is a reduction of muscle strength, balance, muscle endurance, or any combination thereof” is an inherent effect of Ko et al.’s method because the same compound (exenatide) is administered to the same patient populations. There is no additional limitation to the patient population that differentiates it from Ko’s method (such as a patient in need); the claim limitation is just an intended effect.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 [MPEP 2112]
Therefore, Ko et al. anticipates a method for the reduction of muscle strength, balance, muscle endurance, or any combination thereof (a 103 rejection is also made below to establish the GLP-1 agonist’s inherency for improving muscle endurance).
Regarding claim 8, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the aging-associated brain function impairment comprises cognitive impairment. Therefore, Ko et al. anticipates a method of treating a subject for cognitive impairment using exenatide.
Regarding claim 9, Ko et al. does not teach using a GLP-1R agonist to decrease a reduction in muscle endurance. However, the limitation “measurable change in colon activity, adipose tissue amount, circulating white blood cell amount, spleen activity, lung airflow, skeletal muscle activity, heart activity, liver activity, kidney activity, or any combination thereof” is an inherent effect of Ko et al.’s method because the same compound (exenatide) is administered to the same patient populations. There is no additional limitation to the patient population that differentiates it from Ko’s method (such as a patient in need); the claim limitation is just an intended effect.
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999).
There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the relevant time, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 [MPEP 2112]
Therefore, Ko et al. anticipates a method for a measurable change in colon activity, adipose tissue amount, circulating white blood cell amount, spleen activity, lung airflow, skeletal muscle activity, heart activity, liver activity, kidney activity, or any combination thereof (a 102 rejection is also made below to establish the GLP-1 agonist’s inherency for a measurable change in heart activity).
Regarding claim 13, Ko et al. claims the method of treating a subject for aging-associated brain functional impairment, wherein the aging-associated brain function impairment comprises any of measurable structural, functional, and molecular changes of the brain, wherein the aging-associated measurable molecular change is a change in gene expression [claims 10 and 18]. Therefore, Ko et al. anticipates a method for decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a exenatide, wherein the aging-associated functional change is a change in an expression of at least one gene in the subject.
Regarding claim 15, Ko et al. specifies that in certain embodiments, the genes and subsequent transcribed mRNA and translated protein that can be assessed in the subject are immune response-related genes, such as, C1qa [pg 16 line 22]. ]. Therefore, Ko et al. anticipates a method for decreasing an aging-associated functional change in a subject, the method comprising administering to the subject an effective amount of a exenatide, wherein the aging-associated functional change is a change in an expression of the gene C1qa.
Claims 1, 7, and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ding et al (Ding, W., Chang, W. G., Guo, X. C., Liu, Y., Xiao, D. D., Ding, D., Wang, J. X., & Zhang, X. J. (2019). Exenatide Protects Against Cardiac Dysfunction by Attenuating Oxidative Stress in the Diabetic Mouse Heart. Frontiers in endocrinology, 10, 202.).
Regarding claim 1, Ding et al. states that exenatide had cardioprotective effects, in addition to its hypoglycemic effects, such as preventing hepatic steatosis and protecting against cardiac injury from doxorubicin-induced cardiotoxicity or ischemic reperfusion [Abstract line 5]. For example, Ding et al. teaches that the ejection fraction percentages were significantly decreased in type 2 (T2DM) and type 1 diabetes mice (T1DM), compared to the control (CON) mice, but treatment with exenatide restored the heart ejection fraction percentages of type 2 diabetes mice to that of the control group [pg 4 pgh 1 line 12]. A decrease in heart ejection fraction is an aging-associated functional change. Therefore, Ding et al. anticipate a method for decreasing an aging-associated functional change by administering exenatide, as Ding et al. teach that exenatide has cardioprotective effects.
Regarding claim 7, Ding et al. teaches that the ejection fraction percentages were significantly decreased in type 2 (T2DM) and type 1 diabetes mice (T1DM), compared to the control (CON) mice, but treatment with exenatide restored the heart ejection fraction percentages of type 2 diabetes mice to that of the control group [pg 4 pgh 1 line 12]. Therefore, Ding et al. anticipates a method for a decrease in heart ejection fraction using exenatide.
Regarding claim 9, Ding et al. teaches that the EF% (ejection fraction), LVSD (left ventricular end-systolic diameter), and LVDD (left ventricular end-diastolic diameter) were used to determine systolic function, and FS% (fractional shortening) and E/A (ratio of the early (E) to late (A) ventricular filling velocities) were used to determine diastolic function [pg 4 pgh 1 line 1]. Systolic and diastolic dysfunction developed in T2DM and T1DM animals in comparison to CON mice, but exenatide treatment of T2DM animals attenuated this dysfunction. Therefore, Ding et al. anticipates a method for decreasing an aging-associated functional change, measurable by a change in heart activity.
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.
Claims 6 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Wo et al. as applied to claims 1-5, 8, 13 and 15 above, and further in view of Wu et al. (Wu, L., Zhou, M., Li, T., Dong, N., Yi, L., Zhang, Q., & Mi, M. (2022). GLP-1 regulates exercise endurance and skeletal muscle remodeling via GLP-1R/AMPK pathway. Biochimica et biophysica acta. Molecular cell research, 1869(9), 119300.).
While the reduction of muscle strength, balance, muscle endurance, or any combination thereof” is an inherent effect of Ko et al.’s method because the same compound (exenatide) is administered to the same patients (see 102 rejection), Ko et al. does not explicitly teach using a GLP-1R agonist to decrease a reduction in muscle endurance in a patient in need thereof.
Wu et al. demonstrate that GLP-1 enhances physical endurance capacity by inducing skeletal muscle remodeling, which may be mediated by the GLP-1R/AMPK signaling pathway [Introduction pgh 4 line 7] When they assessed whether GLP-1 overexpression would affect muscle endurance using an exhaustive swimming test, they found that the mice showed increased endurance capacity [Section 3.2 pg 1 line 35].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious to administer a GLP-1R agonist, such as exenatide, to a patient in need of increasing muscle endurance.
Regarding claim 9, Wu et al. states,
“Our results showed that over expression of GLP-1 in skeletal muscle enhances endurance capacity. Endurance exercise has been shown to remodel the skeletal muscle, to keep up with the increase in energy demands, thereby improving endurance capacity [25,26]. Skeletal muscle remodeling, such as muscle fiber type switch, muscle mitochondrial content and mass, and energy substrate utilization, determines exercise endurance capacity in turn” [Discussion pgh 3 line 5].
Therefore, prior to the effective filing date, one of ordinary skill in the art would find it obvious that GLP-1 agonists, such as the exenatide taught by Ko et al., would result in a measurable change in skeletal muscle activity because overexpression of GLP-1 results in skeletal muscle remodeling.
Conclusion
Claims 1-9, 13 and 15 are provisionally rejected on the ground of nonstatutory double patenting. Claims 1-5, 13, and 15 are rejected under 35 U.S.C. 112(a). Claim 8 is rejected under 35 U.S.C. 112(b). Claims 1-5, 7-9, 13 and 15 are rejected under 35 U.S.C. 102. Claims 6 and 9 are rejected under 35 U.S.C. 103.
Correspondence
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/SACHI JAUHARI/ Examiner, Art Unit 1654
/CHRISTINA M MARCHETTI BRADLEY/ Primary Examiner, Art Unit 1654
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