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
2. Claims 1 – 10 are pending in this application. Applicant’s preliminary amendment, submitted March 7, 2024, is entered, wherein claims 7 – 9 are amended.
Claims 1 – 10 are examined on the merits herein.
Priority
3. This application is a national stage application of PCT/JP2022/033223, filed September 5, 2022, which claims benefit of foreign priority document JP2021-144496, field September 6, 2021.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/15/2026, 04/28/2026, and 06/04/2026 were filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
The following title is suggested: Heart Disease Agent and Method for Treating Heart Disease.
Claim Objections
Claim 10 is objected to because of the following informalities:
Claim 10, lines 3 – 4, “, the target in need thereof” should be removed and “in need of improving heart disease” should be inserted immediately after “a target” in line 2. Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 10 are 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.
a. Claim 3 recites the limitation "the arrhythmia" in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 3 depends from claim 1 and recites “the arrhythmia”, however, claim 1 never recites “arrhythmia”. It is unclear which arrhythmia” the claim is referring to.
b. Claim 10 recites “(excluding medical practice to human)” in lines 1 – 2. The phrase is written within a parenthesis. It is unclear whether the parenthetical phrase is limiting and is intended to define heart disease or is merely providing non-limiting descriptive information. Thus, the metes and bounds of the claim are not clear and the phrase renders the claim indefinite.
c. Claim 10 recites “causing a target” in line 2. The phrase is indefinite because it is unclear what action is required by the step of “causing” the target to apply the nicotinamide mononucleotide, including whether the claim requires administering the nicotinamide mononucleotide to the target, instructing or inducing the target to self-administer the nicotinamide mononucleotide, or some other act. Accordingly, one of ordinary skill in the art would not be able to determine the metes and bounds of the claimed method with reasonable certainty.
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 – 6 and 8 – 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892).
a. Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claims 4 and 6, the claims are directed to a medicine for heart disease comprising NMN as an active ingredient. Under the broadest reasonable interpretation, the recitations identifying particular arrhythmias in claim 4 and particular diseases caused by arrhythmia in claim 6 describe the intended therapeutic use or intended condition to be improved by the claimed medicine, rather than adding a structural limitation to the medicine itself. The claims do not require a method step of actually treating a patient having each listed arrhythmia or actually improving each listed disease caused by arrhythmia. The claims remain directed to the same NMN-containing medicine. Shen teaches an application of NMN in preparation of a medicament for myocardial ischemia-reperfusion injury, and further teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardiac arrest. Thus, Shen discloses the same active ingredient, NMN, in a medicament for a heart-related disease condition associated with arrhythmia. Because the additional diseases of claims 4 and 6 merely identify the intended use for the same NMN medicine and do not impart a structural difference to the medicine, such limitations do not distinguish the claimed medicine from Shen’s NMN medicament.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
For these reasons above, Shen anticipates the claimed invention.
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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. 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.
Claims 1 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (CN113332304A, Reference included with PTO-892) in view of Weiss (NMN.com, 2020, Reference included with PTO-892).
b. Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
However, Shen does not teach the medicine for heart disease is a food product for improving heart disease.
Weiss discloses that NMN has been formulated as supplementation to promote the health of the cell’s powerhouse, the mitochondria, and prevents heart failure (page 1, para. 2). Thus, Weiss discloses that NMN may be formulated as a supplement, which falls within the claimed “food product” defined in the specification (para. [0032]).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate Shen’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because Shen teaches the same active ingredient, NMN, for improving myocardial ischemia-reperfusion injury and further teaches that the medicament may be provided as an oral formulation and Weiss teaches that NMN had been formulated as a supplement and was known to promote mitochondrial health and prevent heart failure. One would have been motivated to formulate Shen’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because Shen teaches that NMN protects against myocardial ischemia-reperfusion injury by repairing myocardial ischemia-reperfusion injury by repairing myocardial fiber energy metabolism disorder, and Weiss teaches NMN supplementation for promoting mitochondrial health and preventing heart failure. One of ordinary skill in the art would have had a reasonable expectation of success to formulate Shen’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because the proposed modification uses the same active ingredient, NMN, and merely provides Shen’s orally administered NMN in a known supplement/food product form taught by Weiss, without changing the active compound responsible for the disclosed therapeutic effect.
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 and 7 – 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 – 4, and 6 of copending Application No. 18/847,268 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘268 anticipates the claimed invention.
a. ‘268 claims a medicine for oral disease, comprising nicotinamide mononucleotide as an active ingredient (claim 1). ‘268 claims that the medicine is a food product (claim 3) or a medicinal product (claim 4). ‘268 claims a daily amount per adult of the NMN to be applied is 1 mg to 500 mg (claim 6).
Claim 1 of ‘268 claims a composition comprising NMN as an active ingredient. This addresses the presently claimed medicine comprising NMN.
For these reasons above, ‘268 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 9 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3 – 4, and 6 of copending Application No. 18/847,268 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
b. ‘268 claims a medicine for oral disease, comprising nicotinamide mononucleotide as an active ingredient (claim 1). ‘268 claims that the medicine is a food product (claim 3) or a medicinal product (claim 4). ‘268 claims a daily amount per adult of the NMN to be applied is 1 mg to 500 mg (claim 6).
However, ‘268 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘268 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘268 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘268 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘268 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘268 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘268 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘268 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘268 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
Claims 1 and 7 – 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 – 5 of copending Application No. 17/906,194 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘194 anticipates the claimed invention.
c. ‘194 claims a coenzyme Q production accelerator that contains NMN as an active ingredient (claim 1). ‘194 also claims both food product and medicinal product that contains the coenzyme Q production accelerator (claims 4 – 5).
Claim 1 of ‘194 claims a composition comprising NMN as an active ingredient. This addresses the presently claimed medicine comprising NMN.
For these reasons, ‘194 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 9 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4 – 5 of copending Application No. 17/906,194 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
d. ‘194 claims a coenzyme Q production accelerator that contains NMN as an active ingredient (claim 1). ‘194 also claims both food product and medicinal product that contains the coenzyme Q production accelerator (claims 4 – 5).
However, ‘194 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘194 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘194 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘194 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘194 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘194 does not teach a daily amount per adult of the NMN to be applied is 1 mg to 500 mg. ‘194 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘194 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘194 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘194 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 7 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/310,557 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘557 anticipates the claimed invention.
e. ‘557 claims a food that contains an effective dose of NMN (claim 1).
Claim 1 of ‘557 claims a composition comprising NMN as an active ingredient. This addresses the presently claimed medicine comprising NMN.
For these reasons, ‘557 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 8 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 17/310,557 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
f. ‘557 claims a food that contains an effective dose of NMN (claim 1).
However, ‘557 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘557 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘557 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘557 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘557 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘557 does not teach that the medicine is a medicinal product. ‘194 does not teach a daily amount per adult of the NMN to be applied is 1 mg to 500 mg. ‘194 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘557 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘557 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘557 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 7 – 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 – 7 of copending Application No. 17/276,156 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘156 anticipates the claimed invention.
g. ‘156 claims an anti-aging agent that contains NMN as an active ingredient (claim 1). ‘156 claims that the anti-aging agent is a food product or a medical product (claims 6 – 7).
Claim 1 of ‘156 claims a composition comprising NMN as an active ingredient. This addresses the presently claimed medicine comprising NMN.
For these reasons, ‘156 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 9 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6 – 7 of copending Application No. 17/276,156 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
h. ‘156 claims an anti-aging agent that contains NMN as an active ingredient (claim 1). ‘156 claims that the anti-aging agent is a food product or a medical product (claims 6 – 7).
However, ‘156 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘156 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘156 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘156 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘156 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘156 does not teach a daily amount per adult of the NMN to be applied is 1 mg to 500 mg. ‘156 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘156 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘156 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘156 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
This is a provisional nonstatutory double patenting rejection.
Claim 1 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 16/744,692 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘692 anticipates the claimed invention.
i. ‘692 claims a cosmetic composition that contains a NMN (claim 1).
Claim 1 of ‘692 claims a composition comprising NMN. This addresses the presently claimed medicine comprising NMN.
For these reasons, ‘692 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 8 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 16/744,692 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
j. ‘692 claims a cosmetic composition that contains a NMN (claim 1). ‘156 claims that the anti-aging agent is a food product or a medical product (claims 6 – 7). However, ‘692 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘692 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘692 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘692 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘692 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘692 does not teach the composition the medicine is a medicinal product. ‘692 does not teach a daily amount per adult of the NMN to be applied is 1 mg to 500 mg. ‘692 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘692 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘692 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘692 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
This is a provisional nonstatutory double patenting rejection.
Claim 7 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 16/744,692 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892) as applied to claims 1 – 6 and 8 – 10 above, and further in view of in view of Weiss (NMN.com, 2020, See PTO-892).
k. ‘692, Shen, and Xing teach the limitations discussed above.
However, ‘692, Shen, and Xing do not teach the medicine for heart disease is a food product for improving heart disease.
Weiss discloses that NMN has been formulated as supplementation to promote the health of the cell’s powerhouse, the mitochondria, and prevents heart failure (page 1, para. 2).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to formulate ‘692’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because ‘692 teaches a composition containing NMN, Shen teaches the same active ingredient, NMN, for improving myocardial ischemia-reperfusion injury and further teaches that the medicament may be provided as an oral formulation and Weiss teaches that NMN had been formulated as a supplement and was known to promote mitochondrial health and prevent heart failure. One would have been motivated to formulate ‘692’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because Shen teaches that NMN protects against myocardial ischemia-reperfusion injury by repairing myocardial ischemia-reperfusion injury by repairing myocardial fiber energy metabolism disorder, and Weiss teaches NMN supplementation for promoting mitochondrial health and preventing heart failure. One of ordinary skill in the art would have had a reasonable expectation of success to formulate ‘692’s NMN medicament as a food product, such as a supplement, in view of Weiss for improving heart disease because the proposed modification uses the same active ingredient, NMN, and merely provides Shen’s orally administered NMN in a known supplement/food product form taught by Weiss, without changing the active compound responsible for the disclosed therapeutic effect.
This is a provisional nonstatutory double patenting rejection.
Claims 1 and 7 – 8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 16/332,225 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘225 anticipates the claimed invention.
l. ‘225 claims a sleep disorder improving agent that contains a NMN as an active ingredient (claim 1). ‘225 claims that the sleep disorder improving agent is a food product or a medical product (claims 3 – 4).
Claim 1 of ‘225 claims a composition comprising NMN. This addresses the presently claimed medicine comprising NMN.
For these reasons, ‘225 anticipates the claimed invention.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1 – 6 and 9 – 10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 16/744,692 in view of Shen (CN113332304A, See PTO-892) as evidenced by Nair (Journal of Basic and Clinical Pharmacy, 2016, Vol. 7, Issue 2, See PTO-892) and Xing (American Journal of Physiology-Heart and Circulatory Physiology, 2001, Vol. 280, Issue 2, page H684 – H692, See PTO-892).
m. ‘‘225 claims a sleep disorder improving agent that contains a NMN as an active ingredient (claim 1). ‘225 claims that the sleep disorder improving agent is a food product or a medical product (claims 3 – 4).
However, ‘225 does not teach the heart disease is a condition presenting with an arrhythmia, a disease causing an arrhythmia, or a disease caused by an arrhythmia. ‘225 does not teach that the arrhythmia is a bradyarrhythmia or tachyarrhythmia. ‘225 does not teach that the arrhythmia is one of the conditions recited in claim 4. ‘225 does not teach the disease causing an arrhythmia is one of the conditions recited in claim 5. ‘225 does not teach that the disease caused by an arrhythmia is one of the conditions recited in claim 6. ‘225 does not teach a daily amount per adult of the NMN to be applied is 1 mg to 500 mg. ‘225 also does not teach a method for improving heart disease comprising causing a target in need thereof to apply an effective dose of NMN.
Shen teaches an application of nicotinamide mononucleotide (NMN) in preparation of a myocardial ischemia reperfusion injury medicament. According to the technical scheme, active oxygen free radicals are eliminated and/or myocardial fiber energy metabolism disorder is repaired through NMN, so that protection on myocardial ischemia-reperfusion is achieved, and the prevention and treatment effect on myocardial ischemia-reperfusion injury is improved (Abstract). Myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion, and the physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest (page 1, Background, para. 1). Shen also discloses the influence of NMN on myocardial infarction area of MIRI rats. The myocardial infarction area of the NMN administration group rats is obviously lower than that of the model group rats and the myocardial infarction of the rats is reduced along with the increase of the NMN administration dose (page 3, para. 5). The medicament is an oral formulation with the oral dose of NMN between 5 – 25 mg/kg and the injection dosage between 8 – 12 mg/kg (page 2, Detailed Description, para. 6 – 7).
Xing teaches a study that demonstrates ischemia-reperfusion-induced myocardial damage (IRD) is a major factor in the occurrence of ventricular fibrillation during reperfusion after coronary artery occlusion (page H691, Left Col., para. 4).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to apply the composition comprising NMN as an active ingredient as taught by ‘225 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen teaches that a composition comprising NMN is known in the art for improving myocardial ischemia-reperfusion injury. One would have been motivated to apply the composition comprising NMN as an active ingredient as taught by ‘225 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because Shen discloses data that demonstrate the therapeutic effect of NMN for improving myocardial ischemia-reperfusion injury. One of ordinary skill in the art would have had a reasonable expectation of success to apply the composition comprising NMN as an active ingredient as taught by ‘225 for heart disease, such as myocardial ischemia-reperfusion injury, in view of Shen because it is known in the art that NMN is formulated as a medicine for heart disease.
Regarding claim 2, Shen teaches that myocardial ischemia-reperfusion injury causes arrhythmia. Therefore, it read on the limitation “a disease causing an arrhythmia” of claim 2.
Regarding claim 3, Shen teaches that myocardial ischemia-reperfusion injury is likely to occur due to myocardial ischemia/reperfusion and that physiological changes caused by myocardial ischemia-reperfusion injury include arrhythmia, sudden cardiac death, and cardiac arrest. Because bradyarrhythmia and tachyarrhythmia are types of arrhythmia, Shen’s disclosure of arrhythmia encompasses the claimed arrhythmia being a bradyarrhythmia or tachyarrhythmia.
Regarding claim 4, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply Shen’s NMN medicament for myocardial ischemia-reperfusion injury to ischemia-reperfusion-associated arrhythmia, including ventricular fibrillation in view of Xing because Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia and that NMN improves myocardial ischemia-reperfusion injury by reducing myocardial infarction area and improving the prevention and treatment effect on myocardial ischemia-reperfusion injury and Xing further teaches that ischemia-reperfusion-induced myocardial damage is a major factor in the occurrence of ventricular fibrillation during reperfusion. Therefore one of ordinary skill in the art would have had reason to use Shen’s NMN medicament to treat or reduce ischemia-reperfusion injury associated with ventricular fibrillation because Shen teaches improving the underlying ischemia-reperfusion injury and Xing teaches ventricular fibrillation as a specific arrhythmia associated with such ischemia-reperfusion-induced damage. One of ordinary skill in the art would have had a reasonable expectation of success because Shen demonstrates that NMN administration reduces myocardial infarction area in myocardial ischemia-reperfusion injury rats and teaches that NMN provides a protective effect against myocardial ischemia-reperfusion injury.
Regarding claim 6, Shen teaches that myocardial ischemia-reperfusion injury causes physiological changes including arrhythmia, sudden cardiac death, and cardia arrest, and further teaches that NMN improves myocardial ischemia-reperfusion injury by protecting against myocardial ischemia-reperfusion injury and reducing myocardial infarction area. Since claim 6 recites diseases or conditions caused by arrhythmia, one of ordinary skill in the art would have understood that treatment or improvement of myocardial ischemia-reperfusion injury, which Shen teaches causes arrhythmia, would also improve or reduce diseases or conditions resulting from such arrhythmia. Therefore, it would have been obvious to use Shen’s NMN medicament to improve the disease caused by arrhythmia as recited in claim 6.
Regarding claim 9, Shen teaches administration of NMN at an oral dosage of 5 – 25 mg/kg and an injection dosage of 8 – 12 mg/kg. Nair teaches the reference human body weight is 60 kg (page 3, Table 2). Thus, Shen’s oral dosage corresponds to a daily amount of 300 mg to 1500 mg per adult, and Shen’s injection dosage corresponds to a daily amount of 480 mg to 720 mg per adult. These dosage ranges overlap the claimed daily amount of 1 mg to 500 mg per adult.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is found to be allowable.
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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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