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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/06/2026 has been entered.
Status of the Application
Claims 1, 29 and 31-36 are pending and are under current examination.
Maintained Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claim(s) 1, 29 and 31-36 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The subject matter of instant claim 1, is not properly described in the application as filed on 02/17/2021. In particular, there was no indication in original specification as filed or in canceled claims “ humans ---a dosage of 0.2-50mg/Kg body weight” and therefore raise doubt as to possession of the claimed invention at the time of filing.
As reproduced below, the instant specification discloses dosages:
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Applicant is required to cancel the new matter in the reply to this Office Action.
Since the dependent claims 29 and 31-36 doesn’t cure above deficiency, these claims are also rejected failing to comply with the written description requirement.
Maintained Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1, 29 and 31-36 and elected species are rejected under 35 U.S.C. 102(a)(1) and 102 (a)(2) as being anticipated by Sinclair (US 2015/0265642 A1) as evidenced by Walpole (BMC Public Health 2012, 12:439, pages 2-6).
Sinclair discloses a method of treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, , dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims. The cited prior art teaches biochemical mechanism using both cell-based and mouse models that how mitochondrial homeostasis and biogenesis results aging diseases and how NMN reverse aging process by affecting biochemical pathways leading to mitochondrial homeostasis and biogenesis (Figure 17L, paragraphs 0037-0068, Examples, especially examples 7, 8 and 15).
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Paragraphs 0157-0159 (especially 0159) discloses that NMN may be administered in combination with an additional agent for increasing the activity of enzymes involved in NAD+ biosynthesis (involved in mitochondrial biogenesis as evidenced by the instant specification, paragraph 0010 of published application), such as HIF-1alpha inhibitor (NAD+ boosting compound) simultaneously or sequentially.
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With regard to limitations of enhancing mitochondrial proteostasis---mitophagy etc.- Since the cited prior art teaches treating same disease using composition comprising same compounds as in the instant claims, the effect on mitochondria, such as enhancing mitochondrial proteostasis---mitophagy etc., is expected to be the same whether recognized by the cited prior art or not. Thus, the cited prior art reads on the instant claims.
Since the cited prior art reads on all the limitations of the instant claims 1, 29 and 31-36, these claims are anticipated.
Maintained Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 29 and 31-36 and elected species are rejected under 35 U.S.C. 103 as being unpatentable over Sinclair (US 2015/0265642 A1) as evidenced by Walpole (BMC Public Health 2012, 12:439, pages 2-6).
Determining the scope and contents of the prior art
Sinclair discloses a method of treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, , dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims. The cited prior art teaches biochemical mechanism using both cell-based and transgenic mouse models that how mitochondrial homeostasis and biogenesis results aging diseases and how NMN reverse aging process by affecting biochemical pathways leading to mitochondrial homeostasis and biogenesis (paragraphs 0037-0068, Examples, especially examples 7, 8 and 15).
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Paragraphs 0157-0159 (especially 0159) discloses that NMN may be administered in combination with an additional agent for increasing the activity of enzymes involved in NAD+ biosynthesis (involved in mitochondrial biogenesis as evidenced by the instant specification, paragraph 0010 of published application), such as HIF-1alpha inhibitor (NAD+ boosting compound) simultaneously or sequentially.
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With regard to limitations of enhancing mitochondrial proteostasis---mitophagy etc.- Since the cited prior art teaches treating same disease using composition comprising same compounds as in the instant claims, the effect on mitochondria, such as enhancing mitochondrial proteostasis---mitophagy etc., is expected to be the same whether recognized by the cited prior art or not. Thus, the cited prior art meets limitations of the instant claims.
Ascertaining the differences between the prior art and the claims at issue
Sinclair discloses method of treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human NAD+ booster compounds with example of NMN in a dose such as 250mg/Kg-5g/Kg orally in a solid oral formulation of powder) with another agent, such as HIF-1alpha sequentially or simultaneously, wherein the other agent boost NAD+ biosynthesis, i.e., NAD+ boosting compound. However, the cited prior art is silent about reciting HIF-1alpha effect on enhancing mitochondrial proteostasis---mitophagy etc.
Resolving the level of ordinary skill in the pertinent art
With regard to the above difference- Sinclair teaches that NMN may be administered with an additional agent such as HIF-1alpha sequentially or simultaneously, wherein the other agent boost NAD+ biosynthesis. Since NAD+ is involved in mitochondrial biogenesis, any agent that boost biosynthesis of NAD+ is also expected to be involved in mitochondrial biogenesis. Further, as evidenced by the instant specification (paragraph 0010 of the published application) NAD+ boosting compound are included as compounds leading to mitochondrial biogenesis.
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Thus, the cited prior art meets limitation of the instant claims.
Based on the above established facts, it appears that the teachings of above cited prior art read applicants’ process.
Therefore, all the claimed elements were known in the prior art and one skilled person in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention.
Considering objective evidence present in the application indicating obviousness or nonobviousness
To establish a prima facie case of obviousness, three basic criteria must be met: (1) the prior art reference must teach or suggest all the claim limitations; (2) there must be some suggestion or motivation, either in the references themselves or in the knowledge generally available to one of ordinary skill in the art, to modify the reference or to combine reference teachings; and (3) there must be a reasonable expectation of success; and (MPEP § 2143).
In this case, Sinclair discloses method of treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human NAD+ booster compounds with example of NMN in a dose such as 250mg/Kg-5g/Kg orally in a solid oral formulation of powder with another agent, such as HIF-1alpha sequentially or simultaneously, wherein the other agent boost NAD+ biosynthesis.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” (Id. At 1395). See MPEP 2143 - Examples of Basic Requirements of a Prima Facie Case of Obviousness [R-9].
In this case at least prong (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success would apply.
The rationale to support a conclusion that the claim would have been obvious is that “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely that product [was] not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.”KSR, 550 U.S. at ___, 82 USPQ2d at 1397. If any of these findings cannot be made, then this rationale cannot be used to support a conclusion that the claim would have been obvious to one of ordinary skill in the art. Further, there is a reasonable expectation of success that NMN may be administered with another agent, such as NAD+ booster compound and can be made by teachings of the above cited prior art.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited references and to make the instantly claimed process with a reasonable expectation of success.
Response to Arguments
Applicant’s remarks, filed on 01/06/2026, have been fully considered but not found persuasive.
Applicant reiterates all arguments made previously and the Examiner also reiterates same response:
Applicant argues over new matter rejection under 112a:
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This is not found persuasive and the instant claims stand rejected under 112a. This is because as reproduced in the office action and reproduced as below:
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there is no dosage range in the entire paragraph that states range of 0.2-50mg/Kg body weight of human. The paragraph individually recites dose of 50, 60, 70 mg/Kg etc. to any subject, and therefore does not provide support for specific range of 0.2-50mg/Kg body weight in human. Additionally, giving a dose of 400mg/Kg to mice and converting it to 30mg/Kg in human doesn’t support dose range 0.2-50mg/Kg body weight and in humans, when in fact there is no such teaching of range and range for human. Importantly, applicant is in error of identifying example 1, as example 1 is not related to nicotinamide mononucleotide (NMN) but to NR and thus, the example provides no support for any dosage of NMN.
Applicant argues that Sinclair teaching is not specific and uses compound selected from 20 compounds.
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This is not found persuasive and the instant claims are found anticipated and/or obvious over the cited prior art. This is because (1) Sinclair specifically (see cited prior art claims) teaches treating human subject having AD (elected species of Abeta peptide disease) using NMN. Specifically, examples provided by the cited prior art uses NMN as NAD+ booster compound to explain mechanism as well as effect of NMN on ageing and Alzheimer’s disease using in vivo mouse model (see Examples, especially examples 7, 8 and 15). Contrary to applicants’ argument, Sinclair does teach biochemical mechanism using both cell-based and in vivo testing in mice that how mitochondrial homeostasis and biogenesis results aging diseases (same mechanism described by the instant specification) and how NMN reverses aging process by affecting biochemical pathways leading to mitochondrial homeostasis and biogenesis (paragraphs 0037-0068; Examples, especially examples 7, 8 and 15; Figures, and Claims).
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Thus, the cited prior does teach NMN specifically for treating AD. The cited prior art also claims treating AD in humans using NMN; (2) Importantly, Applicant is in error in explaining that the instant specification example 1 uses NMN. In fact, example 1 of the instant specification uses NR and not the compound NMN that applicant is arguing and recited in claim 1; (2) The instant application is broader than the cited prior art and describes over >million compounds, including tetracycline, CD38 inhibitors, PARP inhibitors, statins, compounds modulating lipid metabolism, peptide etc. to treat diseases also >100 diseases including metabolic diseases (itself includes diabetes, Gaucher’s, hemochromatosis (infertility, darkening of skin, joint pain etc.), cardiovascular etc.), low tolerance to injuries, muscle disease, kidney disease, dementia, Parkinson, Huntington, dementia, amyotropic lateral sclerosis etc.; (3) Further, the examples provided in the instant application are with nicotinamide riboside and olaparib in cell based assay Fig 4A-4M and in AD mouse model Fig 5A-5F. Importantly, none of the examples provided by the instant application used NMN, whereas more than 90% of the examples provided by the cited prior art used NMN. Thus, teaching of Sinclair is more specific compared to the instant application; (4) In addition to AD, Sinclair does teach treating other aging diseases as well, such as Parkinson, Huntington, dementia and amyotropic lateral sclerosis using NMN, all of which are recited in the instant claims. This again provides specificity that Sinclair teaches treating ageing diseases using NMN.
With respect to dosage, Sinclair teaches a method of treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, , dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims.
Applicant argues that Sinclair does not teach a range overlapping or touching the claimed range with sufficient specificity.
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This is not found persuasive and the instant claims are found anticipated and/or obvious over the cited prior art. This is because (1) Contrary to Applicants’ argument, Sinclair teaching is more specific towards dosage 250mg/day-5g/day compared to the instant claims. The dosage of instant claims is in fact not even supported by the instant specification. See, for example, new matter rejection. Nowhere the instant specification, recites or supports giving a human a dosage of 0.2-50mg/Kg. Sinclair provides specific range of NMN for treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, , dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims.
Contrary to Applicants’ argument, instant specification is as broad as Sinclair in terms of defining subject. The instant specification provides dose/dosage applicable to any subject, including rat, mice, dogs, cats, humans etc. There is no human dose/ dosage defined in the instant specification (see new matter rejection as set forth above). Sinclair teaching is in fact more specific that it provides teaching of using NMN with that dose with examples Vs. instant application with no such specific dose in humans or even with compound NMN.
Additionally, the instant specification does not provide any teaching of treating human patients in any example. The instant specification gives results from testing in mice, worms and invitro cell-based assay using NR using 400mg/Kg (not even NMN) and then extrapolates that it may be useful in humans.
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The cited prior art also teaches testing in mice and cell-based assays using NMN and then extrapolates that it may be useful in humans. In both cases, i.e., in the instant claims as well as in the cited prior art, teaching in mice and cell- based studies is extrapolated to be useful in human, which is acceptable to office unless applicant shows that study in in vivo mice studies cannot be extended to human then issue of enablement may be raised in the instant claims. Importantly, none of the examples provided by the instant application used NMN even in animals, whereas more than 90% of examples provided by the cited prior art used NMN including in vivo. Thus, Sinclair teaching is in fact more specific.
Applicant argues that the office has read an unclaimed feature into the claims.
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This is again not found persuasive and the instant claims are found anticipated and/or obvious over the cited prior art. This is because (1) Additional teaching of Sinclair of other dose ranges doesn’t preclude that Sinclair teaches dosage of the instant claims. Sinclair provides specific range of NMN for treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, , dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims.
With respect to applicants’ argument over per day. The instant claims are broad to dose/dosage for any interval of time per hour, per day, per week etc. The office has not read any limitation of per day but read claims broadly with respect to any time range and per day is encompassed by broad time range of the instant claims. Further, the dosage range of the instant claims is not supported by the instant specification, especially the range itself, for human as well as for NMN. In addition, applicant is arguing over a single dose which is neither recited in the instant claims nor the instant application, as filed on 02/17/2021.
Applicant argues over rejection under 103:
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This is again not found persuasive and the instant claims are found anticipated and/or obvious over the cited prior art. This is because (1) Sinclair does not have to teach every Alzheimer disease model, every biomarker or prove every theory related to AD; (2) Sinclair teaches same cellular mechanism related to mitochondrial proteostasis as in the instant specification and provides the finding that NMN may be useful in treating AD; (3) Sinclair specifically teaches treating human subject having AD (elected species of Abeta peptide disease) using NMN. Specifically, examples provided by the cited prior art uses NMN as NAD+ booster compound to explain mechanism as well as effect of NMN on ageing and Alzheimer’s disease using in vivo mouse model (see Examples, especially examples 7, 8 and 15). Contrary to applicants’ argument, Sinclair does teach biochemical mechanism using both cell-based and in vivo testing in mice that how mitochondrial homeostasis and biogenesis results aging diseases (same mechanism described by the instant specification and argued by the applicant) and how NMN reverses aging process by affecting biochemical pathways leading to mitochondrial homeostasis and biogenesis (paragraphs 0037-0068; Examples, especially examples 7, 8 and 15; Figures, and Claims).
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Thus, the cited prior does teach NMN specifically for treating AD. The cited prior art also claims treating AD in humans using NMN; (4) Sinclair provides specific range of NMN for treating mitochondrial dysfunction and Alzheimer’s disease, an aging disease comprising administering to a human an NAD+ booster compound with example of NMN in a dose such as 250mg/day-5g/day (see paragraph 0159, 0181) orally in a solid oral formulation of powder (abstract; figures, especially 10A-J, 17A-L, 25-29; paragraphs 0004-0010, 0030-0034, 0140, 0148-0151, 0156-0159, 0170-0184, 0206, 0207, 0220-0221, 0225, 0241, 0265-0268; examples, especially examples 7, 8, 15 using NMN and claims).
As evidenced by Walpole (page 3), global average weight of human is 62Kg, North America average weight of human is 80.7Kg, and Asia average weight of human is weight 57.7Kg.
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Thus, unit dosage of 250mg/day given once/day to human patients (a) when patient has global average weight of 62Kg, 250mg/day for such patient=250mg/62kg= 4.03mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; (b) North America average weight of 80.7Kg, dose of 250mg/day for such patient=250mg/80.7kg= 3.09 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims; and (c) Asia average weight of 57.7Kg, dose of 250mg/day for such patient=250mg/57.7kg= 4.33 mg/Kg; which reads on the dose range 0.2mg/kg-50mg/kg of the instant claims.
Additionally, the instant specification does not provide any teaching of treating human patients in any example. The instant specification gives results from testing in mice, worms and invitro cell-based assay using NR using 400mg/Kg (not even NMN) and then extrapolates that it may be useful in humans.
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The cited prior art also teaches testing in mice and cell-based assays using NMN and then extrapolates that it may be useful in humans. In both cases, i.e., in the instant claims as well as in the cited prior art, teaching in mice and cell- based studies is extrapolated to be useful in human, which is acceptable to office unless applicant shows that study in in vivo mice studies cannot be extended to human then issue of enablement may be raised in the instant claims. Importantly, none of the examples provided by the instant application used NMN even in animals, whereas more than 90% of examples provided by the cited prior art used NMN including in vivo. Thus, Sinclair teaching is in fact more specific.
Lastly, applicant is arguing over limitation “reducing Abeta levels in brain”, which is not recited in the instant claims.
Conclusion
No Claim is allowed.
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/PANCHAM BAKSHI/Primary Examiner, Art Unit 1623
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